CHAPTER
Algae-Based Biologically Active Compounds
6
Muhammad Ibrahim, Mahwish Salman, Shagufta Kamal, Saima Rehman, Aneeza Razzaq, Sajid Hamid Akash Government College University Faisalabad, Faisalabad, Pakistan
6.1 INTRODUCTION Algae are the group of plants known since ancient civilizations. Linnaeus introduced the term algae for the first time in 1753, and in 1789 de Jussieu classified the plants and separated algae from the rest of the plants. This classification is accepted till date [1]. The word “algae” is derived from the Latin word “alga” which means seaweeds [2]. The study of algae is called phycology (phyco means algae and logos means study of). Phycos is a Greek word which means seaweeds. The history of algae is mentioned in the early Chinese, Roman, and Greek literatures. Roman named it Fucus, whereas Chinese called it Tsao. The ancient Hawaiians used algae as food and called them Limu. The algae were used as manure on the north coast of France as early as 12th century [3,4]. They are eukaryotic and predominantly aquatic, photosynthetic organisms, which range in size from tiny flagellate micromonas that is 1 mm (0.000039 in.) in diameter to giant kelps that reach 60 m (200 ft) in length [5]. Biologists divided the living organisms into five kingdoms named as animals, plants, fungus, protists, and prokaryotes [6]. Algae belong to protista kingdom. Protists often share certain morphological and physical characteristics with animals, plants, and fungi. However, protists are neither animals nor plants, and nor fungi [5]. In earlier classifications, algae, which are photosynthetic like plants, were placed in the kingdom planta. Most of the classifications have now removed algae from the plant kingdom due to their simple construction (majority being unicellular), variety of accessory pigments used for photosynthesis, lack of protecting tissue around gametic cells, and their highly varied life histories [7]. Although, algae are photosynthetic organisms, they lack specialized reproductive systems of the plants, which always have multicellular reproductive structures that contain fertile gametes surrounded by sterile cells. Algae also lack true stems, leaves, and roots [5]. Algae are photosynthetic organisms, which contain chlorophyll and other photosynthetic pigments. These pigments trap light energy coming from the sun, convert it into chemical energy, and store it in the form of photosynthetic products such as starch, carbohydrates, and various complex sugars [8]. Their photosynthetic efficiency is higher than other plants, and some species of algae are considered among Algae Based Polymers, Blends, and Composites. http://dx.doi.org/10.1016/B978-0-12-812360-7.00006-9 Copyright © 2017 Elsevier Inc. All rights reserved.
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the fastest growing organisms. It is estimated that photosynthetic efficiency of algae ranges from 3% to 8%, compared to 0.5% of many other terrestrial crops [9]. As the algae cells are complete simple organisms capable of photosynthesis and synthesis of a multitude of other compounds that make up the cell, they have attracted special interest from the biological and phytochemical scientists [10]. The purpose of this chapter is to give brief information about algae and their biologically active constituents. The isolation and characterization of the biologically active components from seaweeds have gained much attention from various research groups across the world and the seaweeds have become a recognized potential natural product in pharmaceutical industries.
6.2 OCCURRENCE Algae have universal occurrence and are found in almost all types of habitats. They are found in freshwater, seawater, on rocks, soil, stones, on other plants and even on animals, in deserts, and on permanent snowfields etc. [11,12]. They sometimes appear in such large quantity that the landscape becomes colored due to the presence of pigments in their cells. The once-mysterious “red snow” is now known to be due to the presence of algae rich in red pigments that mask the green chlorophyll. On the other hand, some algal species grow in hot springs even at a high temperature of 900001 C [13].
6.3 GENERAL CHARACTERS OF ALGAE Algae are chlorophyllous autotrophic organisms [14]. Most of the algae are aquatic; some are terrestrial [14]. They possess thalloid plant body without any variation of plant tissues [14]. They lack vascular tissues (xylem and phloem) and epidermis with stomata [14]. The sex organs are mostly unicellular [14]. Both gametophytic and sporophytic generations are independent in the life cycle of algae [14]. There is no formation of embryo after gametic union [14]. The germination of zygote can be of direct or indirect type [2]. All kinds of reproductions, sexual, asexual, and vegetative, are found in algae [2].
6.4 CLASSIFICATION OF ALGAE Classification is a scientific categorization of organisms in hierarchical series of groups [11]. Harvey is considered as one of the first algologist who gave the first descriptive algal classification [1]. Although different scientists classified algae in a number of ways, according to the structure of algae, it can be classified into two main groups, i.e., microalgae and macroalgae. Microalgae are unicellular organisms, and that means they have only one cell with complex and robust cell walls, whereas macroalgae are multicellular, have complex structures, and look like plants. Based
6.4 Classification of Algae
on the coloring pigments present in macroalgae, they are further divided into three large groups, i.e., red, green, and brown algae [9]. In the older classifications, algae actually were simply divided into four groups, i.e., Phaeophyceae or brown algae, Chlorophyceae or green algae, Rhodophyceae or red algae, and Cyanophyceae or blue-green algae. However, now there is more knowledge about simpler organisms, which were not used to be considered as algae, it has been realized that there is no real reason for such a distinction, and therefore the number of groups is increased. At present, it is most convenient to divide algae into 10e11 classes [15,16]. Generally, algae are categorized into different classes on the basis of nature and properties of pigments, nature of reserve and storage products, type, number, insertion and morphology of flagella, chemical composition and physical features of cell wall, and morphology and characteristics of cells and thalli [10,17].
6.4.1 CHLOROPHYCEAE (GREEN ALGAE) Chlorophyceae or green algae are a large and diverse group of organisms consisting more than 700 species [17]. Green algae occur in wide range of habitants. They are found in aquatic, amphibious, terrestrial, as well as subaerial conditions. They are principally freshwater species but are also found in seawater. Green algae are eukaryotes characterized by chlorophyll a and b as major photosynthetic pigments. Majority of the unicellular green algae contain one chloroplast per cell. They store their food as true starch and have quite rigid cell walls composed of cellulose with pectic substances incorporated into the wall structure. Motile gametes possess two, or multiples of two, equal and terminated inserted flagella [11,13,14,17].
6.4.2 XANTHOPHYCEAE (YELLOW-GREEN ALGAE) Xanthophyceae (yellow-green algae) are represented by 16 genera and 376 species [18]. Most of the members of xanthophyceae are found in free-floating freshwater conditions. Some are found attached to the walls or tree trunks, while others are soil inhabitants. A few representatives are also marine [11,18]. These yellowgreen algae were once classified with the green algae. However, their pale green or yellow-green coloration indicates that they have a unique group of pigments. The main pigment in these algae is xanthophyll along with chlorophyll a and e. Pyrenoids are absent. Reserve food material is oil (glucan and lipids). Their cell walls are composed of cellulose and pectin. Motile gametes possess two or more anterior and unequal flagella, of which larger one is pantonematic-type and smaller is acronematic. In structure xanthophyceae shows similarity with Chlorophyceae [10,11,14,18].
6.4.3 CHRYSOPHYCEAE (GOLDEN ALGAE) Members of this class contain phycochrysin pigment which imparts brown or orange color to the algae. Motile cells possess one or two equal or unequal and dissimilar
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flagella. One of the flagellum is anteriorly directed, long, hairy, and pantonematictype, while the second one is posteriorly directed, short, smooth, and acronematictype. Reserve food material is oil and chrysolaminarin. Cellulose is absent in the cell wall which has a tendency to become silicified [14].
6.4.4 BACILLARIOPHYCEAE (YELLOW OR GOLDEN-BROWN ALGAE) Bacillariophyceae or golden-brown algae are unicellular microorganisms, popularly called as diatoms, containing about 190 genera and are classified into 5500 species [18]. It is the largest unicellular class of algae and most widely spread of all the unicellular algae. It occurs in all types of habitats except in hot waters and extremely dry areas. They are found in both freshwater and salt water and in the moist soil. Abundant in cold waters. The yellow or golden-brown color is due to higher proportion of carotenoids and xanthophylls, diatoxanthin, diadino, and fucoxanthin. Their reserve food material is fat; motile structures are almost absent; and pyrenoids are present. Their cell wall is composed of silica and partially of pectin substances [2,14,18].
6.4.5 CRYPTOPHYCEAE The color of this class varies from brown, red, or olive green to even blue-green due to the presence of different types of pigments. Photosynthetic pigments include biloproteinsddifferent from those of red algae and blue-green algae. They are unicellular, motile, and naked. Flagella are usually equal and located at the anterior end of the cell. Both are band-shaped [14].
6.4.6 DINOPHYCEAE Members of this class, commonly known as dinoflagellates, are dark yellow or brown with characteristic combination of pigments, chlorophyll a and c, and carotenoids (dinoxanthin and peridinin). Members are unicellular and biflagellate. One of the flagellum is acronematic-type whereas the second is in helical form, and described as band shaped. Cells contain many discoid chloroplasts with pyrenoids [14].
6.4.7 CHLOROMONADINEAE Members of this class are bright green in color, unicellular, and biflagellate. Chromatophores are numourous, discoid, and without pyrenoids. Sexual reproduction is absent. Reserve food is fat and oil. The flagella originate from the anterior depression. Of the two, one is anteriorly directed and bears hair, and the second is posteriorly directed and smooth [14].
6.4.8 EUGLENINEAE Members of this class almost resemble to those of Chlorophyceae in having green color, which is due to excess of chlorophyll. The chloroplasts can be discoid or
6.4 Classification of Algae
stellate. Their reserve food material is paramylum, with a number of pantonematictype of flagella, may be 1, 2, or 3. They reproduce by cell division [14].
6.4.9 PHAEOPHYCEAE (BROWN ALGAE) Phaeophyceae or brown algae are represented by about 240 genera and over 1500 species of which 99.7% are marine [11] and live attached to the rocks around sea coasts. They therefore occupy same kinds of habitat as the red algae. Brown algae grow as attached not only to the rocks but also to the dykes, quays-attached mollusks, eelgrass, or even other seaweeds [11,19]. These are multicellular algae and comprise a brown pigment which is responsible for their characteristic brown color and the common name of brown algae or brown seaweeds. They are structurally quite complex [10]. The brown algae owe their color to the pigment fucoxanthin. Fucoxanthin is present in large quantity and masks the green color of the chlorophylls. Other pigments include chlorophyll a, c, b-carotene, violaxanthin, flavoxanthin, etc. Their photosynthetic products are polysaccharides, fats, traces of simple sugars, and alcohols. Food is stored in the form of soluble carbohydrate called laminarin and an alcohol called mannitol. The cell wall is composed of cellulose, fuicinic acid, and alginic acid. The flagellated motile cells are pyriform and bear two laterally borne flagella, of which one is longer, anteriorly directed and pantonematic type and the second one is short, posteriorly directed and acronematic-type [14].
6.4.10 MYXOPHYCEAE (CYANOPHYCEAE) The class Myxophyceae or Cyanophyceae is commonly called as blue-green algae because of the presence of a principal bluish-green pigment (c-phycocyanin) along with chlorophyll a, b-carotene, and some quantity of Myxoxanthin, Myxoxanthophyll as well as small quantities of carotene, flavacin, and c-phycoerythrin [11]. They can be unicellular or multicellular, free-living or colonial, unbranched filamentous or branched filamentous, and acquatic or terrestrial in nature [1]. The bluegreen algae are also known as Cyanobacteria because they resemble to bacteria [19]. The photosynthetic reserve food of blue-green algae is glycogen. Motile flagellated cells are altogether absent, cellular organization is simple prokaryotic type lacking membrane-bound cell organelles such as nucleus, chromatophores, dictyosomes, ER, and true vacuoles. Cells lack definite chromosomes and divide by simple fission [14].
6.4.11 RHODOPHYCEAE (RED ALGAE) The red algae are a distinct lineage of eukaryotic algae, containing about 5000e6000 species [20]. The majority of red algae live in tropical marine habitats, and most of the species are multicellular. Red algae have a complex life history, which means they go through several stages of independent organisms to complete their life cycles. Most undergo sexual reproduction. Like many other
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algae, rhodophytes also contain a phosynthetic pigment chlorophyll and are able to photosynthesize their own food. These algae contain reddish pigment phycoerythrin in a large amount; the red color of these algae is due to the presence of this pigment [21]. Other pigments include chlorophyll a and d, carotenoids (a- and b-carotenes), and xanthophylls (taraxanthin, lutein, zeaxanthin, etc.). Reserve food is stored in the form of floridean starch and galacto-fructosides. Their cell wall is mainly composed of cellulose and pectin, and in addition some components of polysulfate esters of carbohydrates also occur. Majority of the red algae exhibit triphasic life cycles but some also exhibit biphasic life cycles [14].
6.5 BIOLOGICALLY ACTIVE COMPOUNDS EXTRACTED FROM ALGAE 6.5.1 SULFATED POLYSACCHARIDES Sulfated polysaccharides are the polysaccharides present in the cell wall of algae, which play storage and structural roles in seaweeds, and may exhibit many interesting biological properties. Seaweeds are the main source of sulfated polysaccharides [22,23]. The details of these compounds are briefly summarized in Table 6.1.
6.5.2 POLYPHENOLIC COMPOUNDS Phenolic compounds comprise a wide variety of molecules that have a polyphenol structure. Polyphenols are divided into several classes according to the number of phenol rings they contain and the structural elements that bind these rings to one another. The main groups of polyphenols are flavonoids, phenolic acids, tannins (hydrolyzable, condensed, and phlorotannin), stilbenes, and lignans [32].
6.5.3 FLAVONOIDS Flavonoids are the natural products that consist of C6eC3eC6 carbon framework, or more specifically phenylbenzopyran functionality. Depending on the position of the linkage of aromatic ring to the benzopyran moiety, flavonoids can be divided into three classes [33]. • • •
Flavonoids (2-phenylbenzopyrans) Isoflavonoids (3-benzopyrans) Neoflavonoids (4-benzopyrans) The details of these compounds are briefly summarized in Table 6.2.
6.5.4 PHLOROTANNINS Phlorotannins are phenolic compounds formed by polymerization of phloroglucinol (1,3,5-trihydroxybenzene) monomer units and biosynthesized through the
Table 6.1 Sulfated Polysaccharides: Biologically Active Compounds Extracted From Algae Sr. No.
Name
Molecular Formula
Biological Source
Biological Use
1
Heparin
C12H19NO20S3
Red alga Delesseria sanguinea
Anticoagulant, antiinflammatory, and antimetastastic effects
2
Agar
3
Chrysolaminarin
4
Lambda (l)carrageenan
C14H26O19S3
5
Iota (i)carrageenan
C14H24O15S2
Constit. of red seaweed Eucheuma spinosum
Antioxidant
[27]
6
Kappa (k)carrageenan
C14H25O12S
Constit. of red seaweed Kappaphycus alvarezii
Antioxidant
[27]
7
Fucans
Isol. from Analipus japonicas, Ascophyllum nodosum, Chorda filum, Fucus evanescens, and Laminaria saccharina
Anticoagulant
References [24]
[25]
Reserve carbohydrate Antiviral, antioxidant
N/A
[26] [27]
N/A
[27]
Continued
6.5 Biologically Active Compounds Extracted From Algae
Extracted from red marine algae (Rhodophyceae); Gelidiella acerosa, Gelidiella various Gelidium spp. Gracilaria confervoides, Pterocladia capillacea, and Pterocladia lucida Isol. from diatoms and related algae Isol. from species of the Gigartina and Chondrus genera
Structure
161
162
Sr. No.
Name
Molecular Formula
Biological Source
8
Alginate
(C6H8O6)n
Constit. of red and brown algae
9
Ulvan
10
Sulfated mannans
11
Rhamnan sulfate
12
Laminarin
Isol. from cell walls of marine green algae Ulva rigida, Ulva pertusa, and Ulva lactuca Present in red and green seaweeds
Present in cell walls of Monostroma latissimum and Monostroma nitidum
(C6H10O5)n
Constit., constituents; Isol., isolated.
Found in brown algae especially the Laminaria subgroup; isol. from Laminaria cloustoni
Biological Use
Structure
References [28]
Shows cytotoxic props. Antioxidant
N/A
[29]
Inhibit the propagation of HSV-1 in Vero cells Antiviral
N/A
[30]
Anticoagulant; antilipemic agent; plant activator
[31]
[26]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.1 Sulfated Polysaccharides: Biologically Active Compounds Extracted From Algaedcont’d
Table 6.2 Flavonoids: Biologically Active Constituents Extracted From Algae Name
1
40 -Chloro-2-
Molecular Formula C15H11O3Cl
hydroxyaurone
Biological Source Constit. of brown algae Spatoglossum variabile
Biological Use
Structure O
Antioxidant
References [34]
H H
O Cl
2
40 -Chloroaurone
C15H9O2Cl
Constit. of brown algae S. variabile
O
Antioxidant
[34]
O
Cl
3
Morin
C15H10O7
Constit. of green algae Caulerpa serrulata
HO
Antioxidant HO
OH O
4
Hesperidin
C28H34O15
Constit. of red algae
Antioxidant
5
Myricetin
C15H10O8
Constit. of Tubinaria ornate, Chondrus verruscosus
Antioxidant
OH
[35]
O OH
[35]
OH OH HO
O
OH
O
[35]
OH OH
Continued
6.5 Biologically Active Compounds Extracted From Algae
Sr. No.
163
164
Sr. No.
Name
Molecular Formula
6
Quercetin
C15H10O7
Biological Source
Biological Use
Constit. of Undaria pinnatifida and Padina arborescens
Antioxidant
Structure OH HO
(0003)-Catechin (2S,3R)
C15H14O6
Constit. of red alga Acanthophora spicijka
OH
[35]
O
OH
7
References
O
OH
OH
Antioxidant HO
OH
[36]
O OH OH
8
Apigenin
C15H10O5
Constit. of Acanthophora spicifera
Analgesic and antiinflammatory
HO
OH
[37]
CH3
[38]
O
OH O
9
Scutellarein 40 methyl ether
C16H12O6
Constit. of Osmundea pinnatifida
Antileishmanial
O HO HO
Constit., constituents.
O
OH O
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.2 Flavonoids: Biologically Active Constituents Extracted From Algaedcont’d
6.5 Biologically Active Compounds Extracted From Algae
acetateemalonate pathway, also known as polyketide pathway. Phlorotannins are highly hydrophilic components with a wide range of molecular sizes ranging between 126 Da and 650 kDa. Based on the types of linkage, phlorotannins can be classified into four subclasses such as [39]: • • • •
Fuhalols and phlorethols (phlorotannins with an ether linkage) Fucols (with a phenyl linkage) Fucophloroethols (with an ether and phenyl linkage) Eckols (with a dibenzodioxin linkage) The details of these compounds are briefly summarized in Table 6.3.
6.5.5 TERPENES AND TERPENOIDS Terpenes are the hydrocarbons composed of carbon and hydrogen, and are the compounds whose carbon skeleton can be divided into two or more units identical with the carbon skeleton of isoprene. They are formed by bonding the tail of one isoprene unit to the head of another. Terpenes can be oxygenated into terpeneealcohols, terpeneeesters, terpeneeoxides, terpeneeketones, terpeneealdehydes, terpenee esters, and other varieties of oxygenated compounds [71,72]. The details of these compounds are briefly summarized in Table 6.4.
6.5.6 PHYCOBILIPROTEINS Phycobiliproteins (PBPs) are the important photosynthetic accessory pigment biomolecules assembled into a supramolecular light-harvesting antenna complex, phycobilisomes (PBS), in cyanobacteria and red algae [145]. The details of these compounds are briefly summarized in Table 6.5.
6.5.7 STEROLS Sterols are steroids carrying a hydroxyl group at C-3 [146]. Sterols are a type of lipids found in both plants and animals. Although sterols are classified as lipids, they differ significantly from triglycerides and phospholipids in structure and function. Sterol molecules consist of multiple rings made primarily of carbon and hydrogen atoms that are attached to each other [147]. The details of these compounds are briefly summarized in Table 6.6.
6.5.8 POLYHYDROXYALKONATES Polyhydroxyalkonates (PHAs) are polyesters of various hydroxyalkanoates that are synthesized by many gram-positive and gram-negative bacteria in at least 75 different genera. These polymers are accumulated intracellularly to levels as high as 90% of the cell dry weight under conditions of nutrient stress and act as a carbon and energy reserve. The molecular mass of PHAs varies per PHA producer, but is
165
166
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algae
1
2
3
Name 1,2,3,5-Benzenetetrol; 2,5-O-disulfate
1,2,3,5Benzenetetrol,2-Osulfate
1,3,5-Benzenetriol
Molecular Formula C6H6O10S2
C6H6O7S
C6H6O3
4
Benzo[1,2-b:3,4-b0 ]bis [1,4]benzodioxin1,3,6,9,11-pentol
C18H10O9
5
4000 ,7-Bieckol
C36H22O18
Biological Source
Biological Use
Constit. of brown algae Ascophyllum nodosum, Petalonia fascia, Scytosiphon lomentaria, Chorda filum, Fucus distichus spp. anceps, Fucus vesiculosus, Pelvetia canaliculata, and Dictyota dichotoma Constit. of brown algae P. fascia, S. lomentaria, D. dichotoma, A. nodosum, F. vesiculosus, and Himanthalia elongata
Biogenetic precursor of the wide range of oligomeric phlorotannins which are a major component of brown algae
A minor constit. of brown algae, e.g., Halidrys siliquosa, Cystophora retroflexa, Eisenia arborea, Laminaria ochroleuca, Analipus japonicus, Cystophora congesta, and Carpophyllum angustifolium Constit. of brown algae E. arborea, Ecklonia maxima, and Ecklonia stolonifera
Spasmolytic agent, hyaluronidase inhibitor
Constit. of brown algae E. maxima, E. arborea, and Eisenia bicyclis
Structure
References
OH O
O O
HO
OH
O
S O
[40]
S
OH
O
OH
[41,42] O
O S O
OH
OH
HO
OH
HO
[43]
OH
[44]
[45]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
6,60 -Bieckol
C36H22O18
Constit. of brown algae Ecklonia kurome and E. arborea
Antiplasmin inhibitor; a2-macroglobulin inhibitor; exhibits antiHIV activity, antioxidant
[44]
7
8,80 -Bieckol
C36H22O18
Constit. of brown algae E. kurome and E. arborea
Antiplasmin inhibitor; a2-macroglobulin inhibitor, hyaluronidase inhibitor
[44]
8
2,20 ,4,40 ,6,60 Biphenylhexol
C12H10O6
Occurs in several brown algae, e.g., F. vesiculosus, C. retroflexa, C. angustifolium
HO
OH
6.5 Biologically Active Compounds Extracted From Algae
6
[46]
HO
OH HO
9
2-Chloro-1,3,5benzenetriol
C6H5ClO3
Constit. of Rhabdonia verticillata and from brown algae E. arborea and C. angustifolium
OH
Cl HO
[47] OH
167
OH
Continued
Name
Molecular Formula
10
Decafuhalol-A
C60H42O35
Constit. of brown algae Sargassum spinuligerum and C. angustifolium
11
Dieckol
C36H22O18
Constit. of brown algae E. kurome and Ei. bicyclis
12
Difucophlorethol-A
C24H18O12
Isol. from brown algae H. elongata, C. retroflexa, Cystophora torulosa, and Xiphophora chondrophylla
[51,52]
13
Dihydroxyfucotriphlorethol-B
C30H22O17
Isol. from brown algae S. spinuligerum and C. angustifolium
[53]
Biological Source
Biological Use
Structure
References [48]
Inhibitor of a2macroglobulin, glycation and a-amylase
[49,50]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
168
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d
C18H12O9
Constit. of brown algae E. kurome, E. maxima, E. arborea, and Ei. bicyclis
[49]
15
Fucodifucotetraphlorethol-A
C48H34O24
Isol. from brown algae C. torulosa, S. spinuligerum, and C. angustifolium
[53]
16
Fucodiphlorethol-D
C24H18O12
Isol. from brown algae Cystoseira baccata, C. congesta, C. angustifolium, S. spinuligerum, and C. retroflexa
[54]
17
Fucodiphlorethol-D; 4000 -hydroxy
C24H18O13
Isol. from brown algae S. spinuligerum, Carpophyllum maschalocarpum, and C. torulosa
[55,56]
18
Fucodiphlorethol-E
C24H18O12
Isol. from brown algae Durvillaea antarctica, S. spinuligerum, C. torulosa, and F. vesiculosus
[55]
169
Eckol
6.5 Biologically Active Compounds Extracted From Algae
Inhibitor of a2macroglobulin, glycation, and a-amylase
14
Continued
170
Sr. No.
Name
Molecular Formula
Biological Source
Biological Use
19
Fucophlorethol-A
C18H14O9
Constit. of F. vesiculosus
Hyaluronidase inhibitior
20
2,30 ,4,40 ,50 ,6Hexahydroxydiphenyl ether
C12H10O7
Constit. of Bifurcaria bifurcata, Halidrys sp., C. angustifolium, and other brown algae
21
1-C-Methyl-scylloinositol
C7H14O6
Isol. from red alga Polysiphonia fastigiata and brown algae
Structure
References [57]
[58]
OH
[59] OH
HO
OH HO HO
22
4-C-Methyl-myoinositol; D-form
C7H14O6
Isol. from red algae, e.g., P. fastigiata and brown alga, e.g., Laminaria cloustoni
Osmoregulator, especially in brown algae frequently exposed to both fresh water and salt water
OH
[59]
HO
HO
OH
OH
OH
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d
C54H38O31
Constit. of brown algae Sargassum muticum, S. spinuligerum, C. maschalocarpum, and C. angustifolium
[60]
24
Octafuhalol-A
C48H34O28
Constit. of brown algae S. muticum, S. spinuligerum, C. maschalocarpum, and C. angustifolium
[61]
25
Pentafucol-A
C30H22O15
Isol. from brown algae Scytothamnus australis and A. japonicas
[62,63]
26
2,30 ,4,50 ,6Pentahydroxydiphenyl ether
C12H10O6
[64]
27
Pseudoheptafuhalol-B
C42H30O24
Constit. of brown algae including A. japonicus, L. ochroleuca, Sargassum thunbergii, Ecklonia bicyclis, H. elongata, B. bifurcata, Cystoseira tamariscifolia, C. congesta, and S. muticum Constit. of brown algae S. spinuligerum and C. angustifolium
171
Nonafuhalol-A
6.5 Biologically Active Compounds Extracted From Algae
23
[65]
Continued
172
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d Name
Molecular Formula
28
Pseudoheptafuhalol-C
C42H30O24
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
29
Pseudoheptafuhalol-D
C42H30O24
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
30
Pseudohexafuhalol-B
C36H26O21
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
Biological Source
Biological Use
Structure
References
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
Pseudohexafuhalol-C
C36H26O2
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
32
Pseudotetrafuhalol-A
C24H18O14
Constit. of algae C. maschalocarpum and S. spinuligerum
[65]
33
Terfucohexaphlorethol-A
C60H42O30
Isol. from brown algae C. retroflexa, C. maschalocarpum, and C. angustifolium
[52,56]
34
Terfucopentaphlorethol-A
C54H38O27
Isol. from brown algae C. retroflexa and Carpophyllum maschalocarpum
[56]
6.5 Biologically Active Compounds Extracted From Algae
31
173
Continued
174
Sr. No.
Name
Molecular Formula
35
[1,10 :30 ,100 -Terphenyl]-
C18H14O9
Constit. of various brown algae incl. A. japonicus, B. bifurcata, F. vesiculosus, and H. elongate
[45,66]
36
Tetrafucol-A
C24H18O12
Constit. of brown algae F. vesiculosus, A. japonicas, and C. angustifolium
[62]
37
Tetraphlorethol-C
C24H18O12
Constit. of algae L. ochroleuca, C. congesta, E. maxima, Cystophora reflexa, S. spinuligerum, and C. angustifolium
[54]
38
1-(2,4,6Trihydroxyphenyl)5,8,11,14,17eicosapentaen-1-one; (all-Z)-form
C26H34O4
[67]
39
1-(2,4,6Trihydroxyphenyl)-
C24H32O4
Constit. of brown algae Zonaria turneriana, Zonaria diesingiana, Zonaria farlowii, Zonaria tournefortii, and Distromium decumbens Isol. from brown algae Cystophora spp.
2,20 ,200 ,4,40 ,400 ,6,60 ,600 nonol
Biological Source
Biological Use
Structure
References
[68]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d
6,9,12,15octadecatetraen-1one; (all-Z)-form Triphlorethol-A
C18H14O9
Constit. of C. congesta and other brown algae
41
Triphlorethol-B
C18H14O9
Constit. of brown algae E. kurome, E. stolonifera, C. baccata, and C. angustifolium
42
Undecafuhalol-A
C66H46O38
Constit. of brown algae B. bifurcata, Landsburgia quercifolia, C. angustifolium, and S. spinuligerum
Constit., constituents; Isol., isolated.
[69]
Shows antitrypsin and antiplasmin activities
[47]
[70]
6.5 Biologically Active Compounds Extracted From Algae
40
175
176
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algae
1
Name 2-[2-(Acetyloxy)ethenyl]-6,10dimethyl-2,5,9-undecatrienal
Molecular Formula C17H24O3
Biological Source
Biological Use
Penicillus capitatus and Udotea cyathiformis
Antibacterial and ichthyotoxin
Structure
References [73]
O O
2
Adonixanthin
C40H54O3
O OH
Isol. from green algae
[74]
HO O
3
1(10)-Aristolen-9-ol; (ent-9a)-form
C15H24O
Constit. of marine algae
4
9-Aristolen-1-ol; (ent-1b)-form
C15H24O
Constit. of Nardostachys chinensis, Nardostachys grandiflora, and marine algae
5
1,2-Benzenedicarboxylic acid; dibutyl ester
C16H22O4
Reported from Penicillium bilaii. Streptomyces nasri, and Streptomyces melanosporofaciens. Also isol. from various red algae
OH
OH
Insect repellent; now superseded; glycosidase inhibitor
[75]
[76]
[77] O O O O
6
C34 Botryococcene; 1,2,6,7,21,22,24,29Octahydro
C34H66
Constit. of lacustrine sediments attributed to algae
[78]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
7
8
3-Bromo-4,5dihydroxybenzaldehyde
3-Bromo-4,5dihydroxybenzoic acid
C7H5BrO3
C7H5BrO4
Constit. of red algae Polysiphonia spp. and sponge Psammaplysilla purpurea Constit. of Indian algae
Br
Antibiotic
[79]
HO O HO O
OH
OH OH
9
10
3-Bromo-4hydroxybenzaldehyde
C7H5BrO2
3-Bromo-4-hydroxybenzoic acid
C7H5BrO3
Br
Isol. from Asparagopsis taxiformis, P. purpurea, and Rhodomela larix; constit. of Indian algae Constit. of Indian algae
[81]
HO O Br
[82]
HO
O
OH
11
6-(1,3-Butadienyl)-1,4cycloheptadiene; (R)-form
C11H14
Isol. from brown algae Desmarestia aculeata and Desmarestia viridis
Algal gamete sex attractant
[83]
12
3-(1-Butenyl)-4vinylcyclopentene; (3S,4S)-(Z)form, 30 ,40 -Didehydro
C11H14
Isol. from brown algae D. aculeata, D. viridis, and Syringoderma sp.
Algal gamete sex attractant
[84,85]
13
6-Butyl-1,4-cycloheptadiene; (R)-form
C11H18
Isol. from brown algae Dictyopteris spp. and Dictyota dichotoma
[86,87]
177
Continued
6.5 Biologically Active Compounds Extracted From Algae
Br
[80]
178
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
Biological Source
Biological Use Antibiotic, weakly active against gram-positive and gram-negative bacteria and blue-green algae; spore germination inhibitor
Structure
References
14
Colletodiol; 9,10-dihydro, 11,12-diketone
C14H18O6
Constit. of Colletotrichum capsici, Cytospora sp.
15
Crustaxanthin; tetraketone
C40H48O4
Found in fish, crustaceans, bacteria (Mycobacterium laticolum), and algae (Euglena)
[89]
16
b-Cryptoxanthin
C40H56O
Isol. from papaya (Carica papaya) and many other higher plants, also from fungi, diatoms blue-green algae and fish eggs Constit. of diatoms, algae, and fish
[90]
17
Diatoxanthin
C40H54O2
18
2,10-Dibromo-3-chloro-5,10epoxy-8-chamigren-7-ol
C15H21Br2ClO2
[88]
HO
HO
[91,92]
Cl
[93]
HO
19
2,3-Dibromo-4,5dihydroxybenzaldehyde
C7H4Br2O3
3,5-Dibromo-4-hydroxybenzyl alcohol
C7H6Br2O2
Constit. of red algae Laurencia pacifica, Laurencia majuscula, Laurencia nidifica, Laurencia claviformis, and Laurencia marianensis and the mollusk Aplysia dactilomela Isol. from algae Polysiphonia lanosa and R. larix
Feeding deterrent for aphids, insecticide, antimitotic agent
Br
O
Br OH
Br
O
HO
20
Isol. from red algae Polysiphonia spp. and R. larix and Rhodomela confervoides
[94,95] Br
HO
Br
[96]
HO OH Br
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
21
3,4-Dibromo-5-hydroxymethyl1,2-benzenediol
C7H6Br2O3
Isol. from red algae Lenormandia prolifera, Polysiphonia, Odonthalia, and Rhodomela spp.
Br
Glucosidase inhibitor
[79,97]
Br
OH
OH OH
22
24
25
2,4-Dibromophenol
2,6-Dibromophenol
2,6-Di-tert-butyl-4-ethylphenol
C7H10Br2O2
C6H4Br2O
C6H4Br2O
C16H26O
Isol. from red algae Bonnemaisonia hamifera and Bonnemaisonia nootkana Isol. from the acorn worms Balanoglossus carnosus and Ptychodera sp. Commonly found in marine algae, e.g., Grateloupia elliptica, mollusks, and crustaceans Widespread in marine algae, fish, mollusks and crustaceans, such as Barantolla lepte, Marphysa sanguinea, Glycera americana, Lumbrineris latreilli, Nephtys australiensis, Ceratonereis aequisetis, Australonuphis teres, Scoloplos normalis, Penaeus plebejus, Penaeus latisulcatus, Penaeus merguiensis, Platycephalus caeruleopunctatus, Nemadactylus douglasii, Polysiphonia sphaerocarpa, Ulva lactuca, Ptychoderma flava laysanica, and Capitella sp Metabolites of blue-green algae
HO
[98] O Br
Br
Br
Br
[99,100]
OH
Important flavor component of marine fish, mollusks and crustaceans
Br
[101,102]
OH Br
Antioxidant
[103]
6.5 Biologically Active Compounds Extracted From Algae
23
2-(Dibromomethylene) hexanoic acid
HO
179
Continued
180
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
26
2,3-Didehydro-3,30 -dihydroxy-
C40H52O3
b,ε-caroten-4-one
Biological Source
Biological Use
Structure
References
Constit. of Akategani estuarine crab Sesarma haematocheir, green algae, and goldfish
[104]
HO
O OH
27
5,6-Dihydro-3-[2-(4hydroxyphenyl)-2-oxoethyl]2(1H)-pyridinone,
C13H13NO3
Isol. from an algae-infested Caribbean sponge Halichondria melanodocia
OH
O
28
4,18-Dihydroxy-1(9),6,13xenicatrien-19-al
C20H32O3
[105]
O
N H
Brown algae D. dichotoma
[106] HO
HO O
29
3,5-Diiodothyronine; (S)-form
C15H13I2NO4
O
Occurs in proteins of marine algae
HO
[107] NH2
I O I
OH
30
Dilophol
C20H34O
Constit. of algae Dilophus ligulatus and D. dichotoma
[108]
OH
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
Echinenone
C40H54O
Found in echinoids, crustacean and green algae
32
Echinenone; 4-Alcohol
C40H56O
Isol. from blue-green algae
33
Echinenone; 3S-Hydroxy
C40H54O2
Isol. from Adonis annua, Rhizobium lupini, fish eggs, algae
34
Echinenone; 40 -Hydroxy
C40H54O2
O
[109]
HO
[110]
O
[111]
HO
Isol. from the spindle shell Fusinus perplexus, goldfish eggs, green algae, and other spp.
[111]
O
OH
35
Galactaric acid
C6H10O8
Isol. from brown algae, various fruits and fungi
Used as 2% aq. solution to form color complexes with Fe, Co, Cr(III), Mn, U(VI). (pH 3e10)
HO
[112]
OH OH
O HO
O
6.5 Biologically Active Compounds Extracted From Algae
31
HO
Continued
181
OH
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d
36
Name Grahamimycin-B
Molecular Formula C14H20O7
Biological Source Isol. from Cytospora sp.
Biological Use
References
O
[113]
OH O
HO O
O
O
37
1-Heptadecene-4,6,8,10,12pentol; (4S,6S,8R,10R,12R)form, Penta-Me ether
C22H44O5
Isol. from the blue-green algae Scytonema burmanicum and Scytonema mirabile
[114] O O O
O O
38
1-(1,3-Hexadienyl)-2vinylcyclopropane; (1R,10 E,2R,30 Z)-form
C11H16
Constit. of algae Dictyopteris spp.
39
Hyatellaquinone; (þ)-form
C22H30O4
Constit. of Hyatella intestinalis and Spongia sp.; isol. from red algae
[115]
HIV reverse transcriptase (HIV-rt) inhibitor
[116]
O O O OH
40
3-(2-Hydroxy-4,8-dimethyl3,7-nonadienyl)benzaldehyde; Ac
C20H26O3
O
Constit. of green algae Halimeda scabra, Halimeda macroloba, and Halimeda discoidea
[117]
O
O
41
10-Hydroxy-4-oplopanone; (þ)-form
C15H26O2
Constit. of soft coral Nephthea sp. and the algae Laurencia subopposita
42
18-Hydroxy-1(9),6,13xenicatrien-19-al; Ac
C22H34O3
Constit. of marine algae D. dichotoma and Pachydictyon coriaceum
O
[118]
HO
O O O
[106]
CHAPTER 6 Algae-Based Biologically Active Compounds
Weakly active against gram-positive and gramnegative bacteria, and blue-green algae
Structure
182
Sr. No.
7-Isopropyl-1,4dimethylazulene
C15H18
Obtained from essential oils, e.g., chamomile oil; found also in marine red algae and the gorgonians Euplexaura erecta and Alcyonium sp.
44
Isozeaxanthin; diketone
C40H52O2
Constit. of edible mushroom Cantharellus cinnabarinus, sea trout, salmon and brine shrimp, Corynebacterium michiganense also in green algae
45
Lutein
C40H56O2
46
Lycopene
C40H56
47
Cystoseirol-A
C27H36O4
Found in all higher plants, e.g., Mimosa invasiva, Cosmos caudatus, and also in microorganisms e.g., Staphylococcus aureus, green algae, Porphyra spp. Constit. of tomatoes and many other fruits; also occurs in bacteria and fungi; widely distributed in marine algae (red, green and brown) Constit. of brown algae Cystoseira mediterranea, Cystoseira stricta, and Cystoseira tamariscifolia
Antioxidant, inhibits lipid peroxidation; antiinflammatory agent, also used to treat gastrointestinal disorders; hepatoprotectant; immunodepressant; immunomodulatory and antiulcer agent Food coloring
[119]
O
[120]
O
Shows antitumor, antimutagenic and a wide range of antimicrobial activity; potentially useful for treating macular degeneration, antioxidant Used as food coloring
OH
[121]
HO
[122]
[123] O O O OH
48
Mutatochrome
C40H56O
[124]
183
Constit. of orange peel and blue-green algae; also in Calendula officinalis, Capsicum annuum (paprika), Delonix regia, and others
6.5 Biologically Active Compounds Extracted From Algae
43
Continued
Sr. No.
3,10(18)-Pachydictyadiene6,14,15-triol; (1a,5b,6b,11R,14R)-form
Molecular Formula C20H34O3
Biological Source
Biological Use
Structure
References
Isol. from brown algae D. dichotoma and Dictyota indica
[125] OH OH
HO
50
51
Polybromohydroxydiphenyl ethers; 2,30 ,4-tribromo-40 hydroxydiphenyl ether Prasinoxanthin
C12H7Br3O2
C40H56O4
Br
Isol. from Crustose coralline red algae Constit. of algae within Prasinophyceae
Br
Br O
Useful as a chemosystematic marker for algae
[126] OH
[127] O
OH
OH
OH
52
Sargassumketone
C15H18O10
Isol. from brown algae Sargassum kjellmanianum and Sargassum thunbergii
[128]
O
O HO
O O OH
O
O O
OH
53
Siphonaxanthin
C40H56O4
Caulerpa prolifera and other algae belonging to Prasinophyceae
Antiobesity
[129,130]
54
1,4,9,20-Tetraacetoxy1,3(20),6,10,14-phytapentaen19-al
C28H38O9
Halimeda spp. of green algae
Feeding deterrent to fish
[131] O
O O O
O
O
O
O
O
55
2,20 ,3,30 -Tetrabromo-4,40 ,5,50 tetrahydroxydiphenylmethane
C13H8Br4O4
OH
R. larix, R. confervoides, Polysiphonia nigrescens, and Polysiphonia brodiaci
[132] OH Br
Br
Br
OH
Br HO
CHAPTER 6 Algae-Based Biologically Active Compounds
49
Name
184
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d
56
Thyroxine; (S)-form
C15H11I4NO4
O
Thyromimetic, antihypercholesterolaemic
[133]
HO
NH2
I O I I
I OH
57
58
1,5,6-Trichloro-2(dichloromethyl)-6-methyl1,3,7-octatriene; (1Z,3E,5S,6R)-form
C10H11Cl5
9,11,15-Trihydroxyprosta5,13-dienoic acid; (5Z,8R,9S,11R,12R,13E,15S)form
C20H34O5
Isol. from red algae Plocamium cartilagineum and Plocamium coccineum and from mollusk Aplysia limacina Produced by a variety of marine algae and invertebrates, such as Phascolosoma japonica, Haliotis ovina, Crenomytilus grayanus, Modiolus difficilis, Stichopus japonicus, Distolasterias nipon, and Halocynthia aurantium Found in cyanobacteria and most marine algae
59
Zeaxanthin; (3R,30 R, all-E)-form
C40H56O2
60
Brasilenyne
C15H19ClO
Isol. from sea hare Aplysia brasiliana and algae L. nidifica
61
8-Bromo-1,5,6-trichloro-2(dichloromethyl)-6-methyl1,3,7-octatriene; (1Z,3E,5R*,6R*,7E)-form Telfairine
C10H10BrCl5
Constit. of red algae P. cartilagineum and Plocamium suhrii
Cl
[134] Cl
Cl Cl
Cl
OH
Abortifacient, oxytocic and smooth muscle stimulant
[135] OH
OH OH O
OH
[136]
HO
62
C10H14
Constit. of red alga Plocamium telfairia
Shows antifeedant activity
[137]
Cl
Cl
[138,139]
Br Cl Cl
Br
Insecticidal
Cl
[140]
Cl
185
H3C Cl
6.5 Biologically Active Compounds Extracted From Algae
Heterochordaria abietina, Undaria pinnatifida, Sargassum thunbergii, Polysiphonia urceolata, Dendrodoa grossularia, Porphyra umbilicalis, and Enteromorpha intestinalis
Cl CH3
Continued
186
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
63
Sargatriol
C27H38O4
Biological Source
Biological Use
Structure
Constit. of brown alga Sargassum tortile
References [141]
HO OH OH OH
64
Methoxybifurcarenone
C28H40O5
Constit. of brown alga Cystoseira tamariscifolia
65
Astaxanthin
C40H52O4
Constit. of Haematococcus pluvialis
66
4-Bromophenol
C6H5BrO
Marine fish, mollusks, and algae
67
Geosmin
Constit., constituents; Isol., isolated.
C12H22O
Produced by Streptomyces spp. and blue-green algae
[142]
Antioxidant
[143]
OH
[101]
Br
Implicated in off-flavor of shellfish, freshwater fish, drinking water, and some vegetables
HO
[144]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
Sr. No. 1
Name Phycocyanin
Molecular Formula
Biological Source Constit. of bluegreen algae
Biological Use Antioxidative and antiinflammatory
Structure H3C H3C H3C O
2
Phycoerythrin
Constit. of bluegreen algae
N H
H3 C
4
Phycoerythrocyanin
Constit. of bluegreen algae Constit. of bluegreen algae
COO- COO
H3C
[145]
[145] H
N H
N H
N H
O
N/A
[145] SH H
H3C
COO- COO
H
H O
Constit., constituents.
CH3
N O H
H N H
CH3
N
SH H
H
Allophycocyanin
CH3
N H
H3 C
O
3
References
COOHCOOH
N H
[145] H
N H
N H
N H
O
6.5 Biologically Active Compounds Extracted From Algae
Table 6.5 Phycobiliproteins: Biologically Active Constituents Extracted From Algae
187
188
Table 6.6 Sterols: Biologically Active Constituents Extracted From Algae
1
Name Cholesta-5,23-diene3,25-diol; (3b,23E)-form
Molecular Formula C27H44O2
Biological Source
Biological Use
Structure
References
Constit. of red algae Liagora distenta and Scinaia furcellata
HO
[148]
Constit. of red algae L. distenta and S. furcellata
HO
Isol. from brown alga Rhodymenia palmata, red algae Asparagopsis armata, Rissoella verruculosa, and the tetraspora Falkenbergia rufolanosa Constit. of Funtumia latifolia; found in red algae R. palmata and Halosaccion ramentaceum and Patinopecten yessoensis Constit. of Mandevilla pentlandiana and the marine algae Bryopteris pennata and Scinaia fascicularis
HO
OH
2
Cholesta-5,23-diene3,25-diol; (3b,23Z)-form
C27H44O2
[148]
OH
3
Cholesta-5,25-diene3,24-diol; (3b,24S)-form
C27H44O2
4
Cholesta-5,24-dien-3ol; 3b-form
C27H44O
5
Cholesta-5,20,24-trien3-ol; 3b-form
C27H42O
[149]
HO
HO
[150,151]
HO
[152,153]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
6
8
Ergosta-5,24(28)-dien3-ol; 3b-form
Ergosta-5,25-dien-3-ol; (3b,24R)-form
C30H52O
C28H46O
C28H46O
9
Ergosta-5,7,22,25tetraen-3-ol; (3b,22E,24S)-form
C28H42O
10
24Hydroperoxystigmasta5,28-dien-3-ol; (3b,24x)form
C29H48O3
Constit. of Gonyaulax tamarensis, Styela plicata, Sarcophyton glaucum, Holothuria scabra, Pseudostichopus trachus, Synapta maculate, and dinoflagellate sediments Constit. of many marine organisms, such as Eupentacta fraudatrix, Holothuria nobilis, S. maculata, Echinus esculentus, Echinocardium cordatum, Antedon bifida, and Ophiocomina nigra; major sterol of green algae Constit. of Verongia cauliformis, Jaspis stellifera, and Chrysophyte unicellular algae Isol. from the algae Dictylostelium discoideum, Prototheca wickerhamii, and the sponge Ciocalypta sp.
Occurs in dinoflagellates and rarely in other algae, and has been used as a marker of dinoflagellate contribution to organic sediments
Obtained from tunicates Phallusia mamillata, Ciona intestinalis, Turbinaria conoides, and Padina pavonica as well as brown algae
Shows cytotoxic activity
[154]
HO
[155,156]
Cytotoxic HO
[157]
HO
[158]
HO
[159,160]
6.5 Biologically Active Compounds Extracted From Algae
7
4,23-Dimethylergost22-en-3-ol; (3b,4a,5a,22E,24R)form
OH
189
O OH
Continued
Sr. No.
Name
Molecular Formula C29H46O
12
Stigmasta-5,28-diene3,24-diol; (3b,24x)-form
C29H48O2
13
Stigmasta-5,22-dien-3ol; (3b,22E,24R)-form
C29H48O
14
15
Stigmasta-5,24(28)dien-3-ol; (3b,24(28)E)form
Stigmasta-5,24(28)dien-3-ol; (3b,24(28)Z)form
C29H48O
C29H48O
Biological Source Constit. of red algae and Haliclona longleyi; also from green alga Monostroma nitidum Constit. of Sargassum ringgoldianum also from green algae Ulva rigida and Ulva fasciata Constit. of sponges, e.g., Cliona celata, Spheciospongia vesparia, and Haliclona variabilis, green algae Chlorella spp., Ochromonas malhamensis, and clam P. yessoensis Characteristic sterol of brown algae Fucus vesiculosus; also present in Sargassum tortile, Cystoseira sp., Bifurcaria sp., and a marine unicellular alga; also in sponges Stelletta clarella, Tethya aurantia, Lissodendoryx noxiosa, Haliclona permollis, and other Haliclona spp. Major sterol of Callyspongia diffusa and other sponges and some green algae; also found in marine unicellular alga
Biological Use
Structure
References [161] OH
HO
[162,163]
HO
[164,165]
HO
[161]
HO
[161]
HO
CHAPTER 6 Algae-Based Biologically Active Compounds
25-Methylergosta5,7,22-trien-3-ol; (3b,22E,24x)-form
11
190
Table 6.6 Sterols: Biologically Active Constituents Extracted From Algaedcont’d
16
C29H46O
17
Stigmasta-7,9(11),22trien-3-ol; (3b,22E,24S)form
C29H46O
18
Stigmast-5-en-3-ol; (3b,24S)-form
C29H50O
Constit. of Corbicula leana and green algae and higher plants, also isol. from the Phellodendron sp. Constit. of Haloxylon recurvum and marine algae
[166] OH
[167]
HO
Constit., constituents; Isol., isolated.
Constit. of S. vesparia, C. celata, T. aurantia, liverworts, green algae Chaetomorpha aurea, Caulerpa prolifera, Bryopsis plumosa, and Udotea petiolata
[168]
HO
6.5 Biologically Active Compounds Extracted From Algae
Stigmasta-5,7,22-trien3-ol; (3b,24R)-form
191
192
CHAPTER 6 Algae-Based Biologically Active Compounds
generally of the order of 50,000e1,000,000 Da [169]. The details of these compounds are briefly summarized in Table 6.7.
6.5.9 ALKALOIDS The definition of the term alkaloid is not a simple one and is in many cases a source of academic controversy. They constitute a major class of natural products. Alkaloids are nitrogen-containing compounds derived from plants and animals. On the basis of structure, alkaloids are classified into three types [173]. • • •
True alkaloids Protoalkaloids Pseudoalkaloids The details of these compounds are briefly summarized in Table 6.8.
6.5.10 AMINO ACIDS Amino Acids (AA) are defined as organic substances that contain both amino and acid groups. Some amino acid contain two carboxyl groups and some contain two amino groups [196]. The details of these compounds are briefly summarized in Table 6.9.
6.5.11 FATTY ACIDS Fatty acids are the carboxylic acids derived from vegetable oils and animal fats. These are composed of a chain of alkyl groups usually containing an even number (4e22) of carbon atoms and are characterized by a terminal carboxylic group (eCOOH). Their general formula is CH3 (CH2)x COOH. They can be saturated or unsaturated [218]. The details of these compounds have been briefly summarized in Table 6.10.
6.5.12 HYDROCARBONS Hydrocarbons are the compounds composed of only carbon and hydrogen. Alkanes are saturated hyrocarbons, that is, they contain only carbonecarbon single bonds. Those containing one or more carbonecarbon double bonds, triple bonds, or benzene rings are classified as unsaturated hydrocarbon [71]. The details of these compounds are briefly summarized in Table 6.11.
6.5.13 OXYGEN HETEROCYCLES Heterocycles are defined as cyclic molecules that contain one or more heteroatoms in a ring. A heteroatom is an atom other than carbon; common heteroatoms are oxygen, nitrogen, and sulfur. Oxygen heterocycles are compounds that contain
Sr. No. 1
Name Poly-3-hydroxybutyrate (PH3B)
Molecular Formula
Biological Source Blue-green alga Chlorogloea fritschii
Biological Use
Structure CH3
References O
[170]
H O
OH
n
2
Poly(3-hydroxybutyrate-co3-hydroxyvalerate) PHBV
3
Polyhydroxy valerate (PHV)
Produced by the cyanobacterium Nostoc muscorum Agardh Blue-green algae Osxillatoris limosa
[171]
CH2CH3
O
[172]
O n
6.5 Biologically Active Compounds Extracted From Algae
Table 6.7 Polyhydroxyalkonates: Biologically Active Constituents Extracted From Algae
193
Sr. No.
2
Ambiguine-B isonitrile; Deoxy
Ambiguine-D isonitrile
Molecular Formula C26H31ClN2
C26H29ClN2O3
Biological Source
Biological Use
Structure
References
Cl
Blue-green algae Fischerella ambigua, Hapalosiphon hibernicus, and Westiellopsis prolifica
[174,175] N
N H Cl
Blue-green algae F. ambigua and W. prolifica
[174,175]
OH
N
OH
O
N
3
Ambiguine-E isonitrile
C26H29ClN2O2
Cl
F. ambigua, H. hibernicus, and W. prolifica
[174,175]
OH
N
O
NH
4
Ambiguine-G nitrile
C26H27ClN2
Cl
F. ambigua and Hapalosiphon delicatulus
[176] N
NH
5
Biliverdin; 15,16Dihydro
C33H36N4O6
Cyanobacteria and red algae, including Cyanidium caldarium
HO
Chlorophyll d
C54H70MgN4O6
Red algae
NH
NH N
6
[177]
O O
O
HN
HO
O
[14]
CHAPTER 6 Algae-Based Biologically Active Compounds
1
Name
194
Table 6.8 Alkaloids: Biologically Active Constituents Extracted From Algae
7
8
10
11
C10H9Br2NS2
5,12-Dihydrocycloocta [1,2-b:5,6-b0 ]diindole6,13-dicarboxylic acid, Di-Me ester
C24H18N2O4
5,6-Dihydro-3-[2-(1Hindol-3-yl)-2-oxoethyl]2(1H)-pyridinone,
Hordenine
1H-Indole-3-acetic acid
C15H14N2O2
C10H15NO
C10H9NO2
Isol. from red algae Laurencia brongniartii and Laurencia grevilleana Green algae Caulerpa serrulata, Caulerpa racemosa, Caulerpa sertularioides, Caulerpa taxifolia, Caulerpa cuppresoides, Caulerpa scalpelliformis, Caloglossa leprieurii, and Laurencia majuscule Isol. from an algaeinfested Caribbean sponge Halichondria melanodocia Anhalonium fissuratum, Hordeum vulgare; also present in the Amaryllidaceae, Gramineae, Leguminosae, and algae and fungi including marine alga Phyllophora nervosa
[178]
S S N H
Br
O
Plant growth regulator, phycotoxin, vermifuge
N H O
O H N
[179,180]
O
H N
[181]
O O HN
Diuretic, disinfectant, antihypotensive (in large doses) agent; used for treatment of dysentery; feeding repellant for grasshoppers; shows similar actions to 2(methylamino)-1phenyl-1-propanol Plant growth hormone (auxin); involved in root development; phytotoxic agent
[182]
N
OH
O HN
OH
[183]
195
Isol. from the marine alga Undaria pinnatifida, also in bacteria, yeasts, and fungi
Br
6.5 Biologically Active Compounds Extracted From Algae
9
4,6-Dibromo-2,3bis(methylthio)-1Hindole
Continued
196
Table 6.8 Alkaloids: Biologically Active Constituents Extracted From Algaedcont’d
12
13
Name
Molecular Formula
1H-Indole-3-carboxylic acid
C9H7NO2
1H-Indole-3-ethanol; O-b-D-Glucopyranoside
C16H21NO6
Biological Source
Biological Use
Structure
References
OH
Present in apple, garden pea, Brassica spp., and the marine algae U. pinnatifida and Botryocladia leptopoda Isol. from numerous plant and algae
[183]
O
NH
H N
HO
OH OH
[184]
O
HO
O
14
10 -Methylzeatin; (R)form, 2-Hydroxy
C11H15N5O2
15
2-Phenylethylamine
C8H11N
16
Phycocyanobilin
C33H38N4O6
Produced by Alternaria brassicae and isol. from marine green algae
Shows cytokinin activity; plant growth stimulator
Acacia spp., Crataegus spp.; also present in animal tissues, some algae, fungi and cacti (Leguminosae, Rosaceae, Cactaceae). Metab. of Prosopis alba Phormidium luridum, Synechococcus lividus, and Plectonema boryanum; also present in red algae
Shows DNA binding activity. Monoamine oxidase inhibitor
N
H N
[185]
NH N
N
OH OH
NH2
HO
O
H N
[186]
O
[187] H N N
HO O
O NH
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
17
Phycoerythrobilin
C33H38N4O6
Blue-green algae as well as most red algae
O
N
H N
NH O
20
C6H9NO4
Saxitoxin; N1-Hydroxy
C10H17N7O5
2,3,5,6-Tetrabromo1H-indole
C8H3Br4N
Thallusin
C25H31NO7
Constit. of Mediterranean red algae Chondria coerulescens, Chondria dasiphylla, and Ceramium rubrum Found in shellfish, marine algae, and other organisms incl. Gonyaulax tamarensis, Saxidomus giganteus, Vibrio sp., Pyrodinium sp. L. brongniartii and Laurencia similis
H N
O
[189]
O
O
6.5 Biologically Active Compounds Extracted From Algae
19
2,4Pyrrolidinedicarboxylic acid; (2S,4R)-form
[188]
O
NH
18
OH
OH
OH OH
Neurotoxic neuromuscular blocker
NH HN
O O
NH2 HO
N
NH
[190] OH OH
N
HN
H N
Br
[191] Br
Br Br
21
Isol. from a marine bacterium Cytophaga sp. YM2-23 obt. from a Monostroma sp.
O
Morphogenesis inducer in algae
OH N
OH OH O
22
C21H21ClN2O2S
Blue-green algae Hapalosiphon welwitschii and Westiella intricata
O
Cl
N S
[193]
197
Welwitindolinone-B isothiocyanate
[192] O
O O N H
Continued
198
Sr. No.
Name
Molecular Formula
23
Zeatin; (E)-form
C10H13N5O
24
Adenosine diphosphate glucose
Constit., constituents; Isol., isolated.
C16H25N5O15P2
Biological Source
Biological Use
Isol. from sweet corn Zea mays and numerous other plants; also from algae, bacteria, and basidiomycetes Present in ripening cereal grains; also obt. from algal cells
Induces cell division; most effective of all known natural cytokinins; nematicide Serves as the glycosyl donor for formation of bacterial glycogen, amylose in green algae, and amylopectin in higher plants
Structure N
H N
References [194]
NH N
N OH
OH
HO
[195] O
HO
O HO P O
HO
N
N
O
O
H2N N
OH P O O
N HO
OH
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.8 Alkaloids: Biologically Active Constituents Extracted From Algaedcont’d
Table 6.9 Amino Acids: Biologically Active Constituents Extracted From Algae Sr. No. 1
Name 3-Aminopropanoic acid
Molecular Formula C3H7NO2
N2-Arginylglutamine; LL-form
C11H22N6O4
3
Chondrine; (1S,3S)form
C5H9NO3S
Gigartinine; (S)-form
C7H15N5O3
4
5
Gongrine
C6H12N4O3
Widely distributed in plants including algae, fungi, and many higher plants Isol. from Euglena gracilis and from the green algae Cladophora spp., Enteromorpha linza, and Ulva pertusa Red alga Chondria crassicaulis, brown alga Undaria pinnatifida Constit. of many spp. of red algae, e.g., Gymnogongrus flabelliformis, Gelidium amansii, Grateloupia livida, Grateloupia filicina, Polyopes polyideoides, Carpopeltis flabellata, Hypnea japonica, and Gracilaria textorii Isol. from red algae G. flabelliformis and G. filicina
Biological Use
Structure
References
Catalyst for Knoevenagel condensations. Used for synthesis of Pantothenic acid and derivatives
HO
[197] O
NH2
[198,199]
O
OH
[200,201]
NH S
O
H N
O
NH2
[202]
NH NH H2N O OH
H N
O
NH2
[203,204]
NH NH HO O
6
Methionine sulfoxide; (S)C(R)S-form
C5H11NO3S
O H2N
[205] OH
O S
Continued
199
Isol. from various red algae incl. Amphiroa beauvoisii and Grateloupia proteus
6.5 Biologically Active Compounds Extracted From Algae
2
Biological Source
Sr. No.
8
9
10
11
12
Methionine sulfoxide; (S)C(R)S-form, N-Me
N-(2-Sulfoethyl)alanine; (R)-form
Molecular Formula C6H13NO3S
C5H11NO5S
1,2,3,6-Tetrahydro-2pyridinecarboxylic acid; (S)-form
C6H9NO2
N-Trimethyllysine betaine; (S)-form
C9H20N2O2
Citrulline; (S)-form
C6H13N3O3
Domoic acid
C15H21NO6
Biological Source Isol. from various red algae incl. Centroceras clavulatum, Grateloupia doryphora, and Gelidium latifolium Isol. from algae Chondrus ocellatus and Rhodoglossum japonicum Present in Baikiaea plurijuga, Caesalpinia tinctoria, red algae also in Russula subnigricans Green alga Enteromorpha intestinalis, brown algae Laminaria angustata, and Heterochordaria abietina; also from the seaweed Petalonia fascia Occurs in the watermelon Citrullus vulgaris, green alga E. intestinalis, and red alga G. filicina; widely distributed in Cucurbitaceae and fungi Constit. of red algae Chondria armata and Alsidium corallinum
Biological Use
Structure
References
O
H N
[205,206] OH
O S
H N HO
Neurotransmission inhibitor
Intermediate in biosynthesis of carnitine and g-butyrobetaine; cell proliferation stimulant. Antihypertensive and hypocholesterolemic agent Diuretic agent; used as arginine substitute in the treatment of inborn errors of urea synthesis, carbamyl phosphate synthetase and ornithine transcarbamylase deficiency Ionotropic glutamate (kainate) receptor agonist; neurotoxin. amnesic shellfish poison; vermifuge, insecticide
OH S O O
O
O
OH
[207,208]
[205,209]
HN
NH 2 N+
-
O
NH2
HN H2N
O HO
H N
[205]
O
OH O OH
[211]
O
OH O
[210]
O
CHAPTER 6 Algae-Based Biologically Active Compounds
7
Name
200
Table 6.9 Amino Acids: Biologically Active Constituents Extracted From Algaedcont’d
13
14
16
C10H15NO4
2,5Pyrrolidinedicarboxylic acid; S,5S)-form
C6H9NO4
4-Hydroxy-2pyrrolidinecarboxylic acid; (2R,4R)-form, NMe
C6H11NO3
2-Aminoethanesulfonic acid
C2H7NO3S
Constit. of red algae Alsidium helminthochorton, C. clavulatum, and Digenea simplex Reported from red algae Schizymenia dubyi and Haematocelis rubens Constit. of Capsicum annuum, Copaifera spp., Croton gubougia, Dalbergia sympathetica, Erythroxylum argentinum, Toddalia aculeate, and Afrormosia elata; also from red alga Chondria coerulescens and other red algae Occurs in animal tissues, bacteria, sponges, and red algae, e.g., isol. from Macrocallista nimbosa, Turbo stenogyrus, Calyx nicaeensis, Geodia gigas, Mytilus edulis. Also from green algae, e.g., Caulerpa okamurai, Caulerpa racemosa, Chlorodesmis comosa, Codium adherens, Codium fragile, and E. linza; and from higher plants, e.g., leguminous seedlings
O
Glutamate receptor agonist; neurotoxin, formerly used as an anthelmintic agent
[205]
OH OH N H
O
O
[205]
H N
HO
O
6.5 Biologically Active Compounds Extracted From Algae
15
Kainic acid
OH
N
O HO
[212]
OH
HO
Used as an adjunct in treatment of hypercholesterolaemia; metabolic regulator
O
O S
[213] NH2
201
Continued
202
Sr. No. 17 18
19
20
21
Molecular Formula
Biological Source
2-Aminoethanesulfonic acid; N,N-Di-Me
C4H11NO3S
Furcellaria fastigiata
2-Aminoethanesulfonic acid; N-Me
C3H9NO3S
2-Amino-3-hydroxy-1propanesulfonic acid; (S)-form
C3H9NO4S
Name
3-Amino-1propanesulfonic acid
2,5-Diaminopentanoic acid; (S)-form
Constit., constituents; Isol., isolated.
Biological Use
Structure O
O
[214]
S
N
HO
C3H9NO3S
C5H12N2O2
Red alga Ptilota pectinata and green alga C. comosa. Isol. from brown (e.g., Hijikia fusiforme) and green (U. pertusa, E. linza) algae. Also from diatoms, e.g., Navicula pelliculosa and starfish Asterina pectinifera Constit. of marine red algae, e.g., G. livida and from green alga Cladophora densa
Isol. from green algae Codium decorticatum, E. intestinalis, and Ulva lactuca
O
References
O S
[215] N H
HO
O HO S O
[59] NH2 OH
Inhibits amyloid A fibril formation and deposition; used in the treatment of Alzheimer disease and cerebral amyloid angiopathy Used in treatment of hyperammonemia and liver disorders
NH2
HO O S O
H2N HO
[216]
NH2 O
[217]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.9 Amino Acids: Biologically Active Constituents Extracted From Algaedcont’d
Table 6.10 Fatty Acids: Biologically Active Constituents Extracted From Algae Sr. No. 1
3
4
Molecular Formula
3-Bromo-2-heptenoic acid; (E)form
C7H11BrO2
(2-Carboxyethyl) dimethylsulfonium(1þ)
C5H11O2S1þ
13-(2-Cyclopentenyl)tridecanoic acid; x-form, 20 ,30 -dihydro
C18H34O2
11-(2-Cyclopentenyl) undecanoic acid; (þ)-form, 20 ,30 -dihydro
C16H30O2
Biological Source Constit. of red algae Bonnemaisonia hamifera and Bonnemaisonia nootkana Isol. from green and red algae, e.g., Enteromorpha intestinalis, Ulva lactuca; also from Spartina anglica Constit. of Hydnocarpus anthelmintica and various red algae of Solieriaceae
Biological Use
Structure
References
O Br
Biological precursor of Dimethyl sulphide; fish feeding stimulant
[219]
OH
S+
[220]
OH O
[221]
O HO
Constit. of H. anthelmintica and various red algae of Solieriaceae
[221]
O HO
5
6
2-(Dibromomethylene)octanoic acid
5,7,9,14,17-Eicosapentaenoic acid; (5E,7E,9E,14Z,17Z)-form
C9H14Br2O2
C20H30O2
Isol. from red algae Bonnemaisonia spp. Isol. from red algae Murraya periclados and Ptilota filicina
Br
[222]
Br
O HO
O OH
[223,224]
Continued
6.5 Biologically Active Compounds Extracted From Algae
2
Name
203
204
Table 6.10 Fatty Acids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
5,8,11,14,17-Eicosapentaenoic acid; (all-Z)-form
C20H30O2
8
7,10,13-Hexadecatrienoic acid; (Z,Z,Z)-form
C16H26O2
9
3-Hexadecenoic acid; (E)-form
C16H30O2
10
2-Oxohexadecanoic acid
C16H30O3
7
11
12
12,13-Dihydroxy-5,8,10,14,17eicosapentaenoic acid; (5Z,8Z,10E,12R,13S,14Z,17Z)form
C20H30O4
13-Hydroxy-5,8,11,14,17eicosapentaenoic acid; (all-Z)form, Et ester
C22H34O3
Biological Source Present in fish oils, in animal phospholipids, and constit of various red algae
Present in a wide variety of angiosperm leaves and green algae; isol. from the sponge Dysidea fragilis Constit. of spinach leaves, red clover, Grindelia oxylepis, and Helenium bigelovii; also isol. from algae Constit. of algae Porphyra sp. and Ulva pertusa Constit. of red algae Farlowia mollis and Gracilariopsis lemaneiformis Isol. from a mixture of algae Lithothamnion calcareum and Lithothamnion corallioides
Biological Use Nutriceutical with antioxidation props; precursor of PG3 series of prostaglandins; platelet aggregation inhibitor; allelopathic agent
Structure
References
O
[225] OH
HO
HO
O
[226]
O
[227]
HO
O
[228]
O
OH
[229]
OH
O OH
O O
OH
[230]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
13
15
16
C20H32O3
8-Hydroxy-13-oxo-5,9,11,14eicosatetraenoic acid; (5Z,8x,9E,11E,14E)-form
C20H30O4
2-Propenoic acid
C3H4O2
13-Octadecenoic acid; (Z)-form
Constit., constituents; Isol., isolated.
Found in red algae Murrayella periclados and Platysiphonia miniata, and sponge Echinochalina mollis Isol. from the algae Lithothamnion spp.
Immunohormone; cell growth inhibitor; proinflammatory agent; toxic to brine shrimp
OH
[224]
O
HO
HO O
[230]
O OH
C18H34O2
Found in green algae; produced by Phaeocystis sp., Phaeocystis pouchetii, Enteromorpha sp., Ulva sp., Codium sp., Patinopecten yessonensis, and Protogonyaulax sp. Constit. of algae, bacteria, fish; also found in various plant spp.; isol. from Haliclona cinerea
OH
[226]
O
HO
O
[231]
6.5 Biologically Active Compounds Extracted From Algae
14
12-Hydroxy-5,8,10,14eicosatetraenoic acid; (5Z,8Z,10E,12S,14Z)-form
205
206
Table 6.11 Hydrocarbons: Biologically Active Constituents Extracted From Algae
1
2
3
Name Bromochloromethane
Bromodichloromethane
Bromoiodomethane
Molecular Formula CH2BrCl
CHBrCl2
CH2BrI
4
Bromomethane
CH3Br
5
Carbon tetrabromide
CBr4
6
Carbon tetrachloride
CCl4
Biological Source Isol. from several marine algae Isol. from several marine algae Isol. from several marine algae Isol. from various marine sources incl. giant kelp and ice algae.
Isol. from various marine algae including Asparagopsis taxiformis Isol. from several plants and marine algae
Biological Use
Structure
References
Intermediate for organic synthesis, fire extinguishant Source of dichlorocarbene on treatment with base
Cl
[232] Br
Cl
Br
[232,233]
Cl
Br
[232,234] I
Principally used as an insecticidal and nemacidal fumigant, especially for soil and agricultural produce
Br
[232,234]
Br Br
Br
[232,234]
Br
Cl
Anthelmintic Cl
[232,234] Cl
Cl
7
8
9
10
Chloroform
Chloroiodomethane
Dibromochloromethane
Dibromoiodomethane
CHCl3
CH2C11
CHBr2Cl
CHBr2I
Found in various plants and algae
Isol. from phytoplankton and various marine algae Isol. from several marine algae including A. taxiformis Isol. from several marine algae including A. taxiformis
Formerly used as anesthetic. Topical remedy for Herpes simplex sores Versatile organic synthon. Commercially available Source of bromochlorocarbene in the presence of base and crown ether
Cl Cl
[232,234] Cl
I
[232,234]
Cl
Br Cl
[232,234] Br
Br I
[232,234] Br
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
11
12
Dichloromethane
Diiodomethane
CH2Br2
CH2Cl2
CH2I2
14
Ethylamine
C2H7N
15
3,6,9,12,15,18Heneicosahexaene; (allZ)-form
C21H32
16
C21H34
17
3,6,9,12,15Heneicosapentaene; (all-Z)-form 1-Hexacosene
C26H52
18
1-Iodobutane
C4H9I
Isol. from various marine algae including red alga A. taxiformis Found in various plants and algae and in volcanic gases
Br
Widely used solvent used in coffee decaffeination. Component of paint removers. Blowing agent in foams. Can replace formaldehyde as reagent for Mannich reagents
Cl
[232,234] Br
[232] Cl
I
[234] I
Used in manufacture of resins, rubber, herbicides, etc.
H 2N
[235]
[236]
[237,238]
[239]
Used to esterify fatty acids for GC analysis
[232] I
Continued
207
Isol. from various marine algae Produced by marine algae, Clostridium spp., Candida albicans, Brevibacterium linens and Streptococcus lactis Isol. from marine algae and plankton, e.g., Rhizosolenia setigera and Skeletonema costatum Constit. of Polytrichum commune and benthic green algae Constit. of Acanthopanax giraldii, Aralia elata, Hippophae rhamnoides and various algae incl. Chlorella sp. Isol. from several marine algae
Solvent, reagent for organic synthesis
6.5 Biologically Active Compounds Extracted From Algae
13
Dibromomethane
208
Sr. No.
Name
Molecular Formula
19
Iodoethane
C2H5I
20
Iodomethane
CH3I
21
7-Methylheptadecane
C18H38
22
3,6,9,12,15Nonadecapentaene; (allZ)-form
C19H30
23
Pentadecane
C15H32
24
3,6,9,12Pentadecatetraen-1yne; (3E,6Z,9Z,12Z)form
C15H20
25
3,6,9-Pentadecatrien-1yne; (3E,6Z,9Z)-form
C15H22
Biological Source
Biological Use
Structure
References
Isol. from several marine algae Isol. from marine algae and giant kelp.
Used to esterify fatty acids for GC analysis Methylating agent, Soil fumigant, insecticide, acaracide, rodenticide and fungicide
I
[232]
I
[232]
Isol. from various bluegreen algae including Anabaena sp. and Nostoc sp. Found in marine benthic algae
[240]
Blue-green algae Oscillatoria splendida, Oscillatoria amoena, Oscillatoria geminate, Rumex japonicas, Vallisneria denseserrulate, and Aphanizomenon sp. Isol. from Laurencia okamurai
[238]
Constit. of L. okamurai
[238]
Possible precursor of a wide range of C-15halogenated cyclic ethers found in marine red algae Possible precursor of a wide range of C-15halogenated cyclic ethers found in marine red algae
[241]
[242]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.11 Hydrocarbons: Biologically Active Constituents Extracted From Algaedcont’d
26
Tribromomethane
CHBr3
1,3,5,8Undecatetraene; (3E,5Z,8Z)-form
C11H16
28
1,3,5-Undecatriene; (3E,5Z)-form
C11H18
Constit., constituents; Isol., isolated.
Antitussive; sedative, solvent for waxes, greases, and oils Smelling principle of the gametes of brown algae Spermatochnus paradoxus; sperm attractant of the marine brown alga Ascophyllum nodosum
Br Br
[243,244] Br
[245,246]
[247]
6.5 Biologically Active Compounds Extracted From Algae
27
Constit. of red algae Asparagopsis spp. and Falkenbergia rufolanosa Constit. of the algae of the genera Dictyopteris, Dictyosiphon and Spermatochnus; also occurs in mandarin and tangerine oranges and pineapple Occurs in algae Cystophora siliquosa and Dictyopteris sp.; isol. from the fruit of Ananas comosus (pineapple)
209
210
CHAPTER 6 Algae-Based Biologically Active Compounds
oxygen as a heteroatom in the ring [248]. The details of these compounds are briefly summarized in Table 6.12.
6.5.14 ALCOHOLS Alcohol is a class of compound containing eOH (hydroxyl) group. Alcohols are important because they can be converted into other types of compounds, including alkenes, haloalkanes, aldehydes, ketones, carboxylic acids, and esters. Thus alcohols play a central role in the interconversion of organic functional groups [71]. The details of these compounds are briefly summarized in Table 6.13.
6.5.15 LIPIDS Lipids are a heterogeneous group of naturally occurring organic compounds, classified together on the basis of their common solubility properties. Lipids are insoluble in water but soluble in nonpolar, aprotic organic solvents [71]. The details of these compounds are briefly summarized in Table 6.14.
6.5.16 CARBONYL COMPOUNDS Carbonyl compounds contain a carbonyl group C]O in their molecules. Carbonyl group is the functional group of aldehyde and ketone and is one of the important functional groups in organic chemistry [71]. The details of these compounds are briefly summarized in Table 6.15.
6.5.17 OTHERS Various other compounds have also been isolated from different species of algae. The details of these compounds are briefly summarized in Table 6.16.
6.6 THERAPEUTIC APPLICATIONS OF ALGAE Scientists all across the world are trying to resolve the relationship between structure and therapeutic activities of algal-sulfated biopolymers. A spate intrigue has been observed to dab unexploited aquatic channels for the improvement of innovative therapeutics as algal cell wall polysaccharides and phytoconstituents have revealed a miraculous biological capital. The pharmacological properties of algae and their mode of action are reviewed as under.
6.6.1 ANTICOAGULANT ACTIVITY Anticoagulant properties were first discovered in the extracts of marine algae over 50 years ago. The major active compounds are a variety of sulfated polysaccharides,
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algae Sr. No.
Name
Molecular Formula
1
1,5-Anhydrofructose; D-form
C6H10O5
Biological Source
Biological Use
Exists in rat liver, fungi, and algae
Antioxidant
Constit. of Lilium spp., Euonymus europaeus, Capsicum annuum, and Chrysophyceae algae Isol. from Viola tricolor, Lonicera japonica, Delonix regia, and other plants; present in red algae Present in red algae
Potential nutriceutical
Structure O
3
HO
Auroxanthin
Auroxanthin; 3,30 -Dideoxy
C40H56O3
C40H56O4
C40H56O2
OH
[250]
O
OH
HO
[251] O HO
O
6.6 Therapeutic Applications of Algae
4
Antheraxanthin; (3S,30 R,5S,6R,9Z)-form
[249]
O OH
2
References
HO
[251] O O
5
6
Cystoseirol-A
1-O-(6-Deoxy-6sulfoglucopyranosyl)glycerol; a-D-form, 3-Hexadecanoyl
C27H36O4
C25H48O11S
[123] O O O OH
[252]
211
Constit. of brown algae Cystoseira mediterranea, Cystoseira stricta, and Cystoseira tamariscifolia Isol. from Anthocidaris crassispina, brown algae Sargassum thunbergii, and Sargassum wightii; and red alga Caulacanthus ustulatus
Continued
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algaedcont’d
7
Name
C20H32O3
8
1,6-Di-O-b-Dglucopyranosyl-D-mannitol
C18H34O16
9
2,3-Dihydroxypropanoic acid; (R)-form, 2-O-a-DMannopyranoside
C9H16O9
10
2,3-Dihydroxypropyl [5deoxy-5-(dimethylarsino)] ribofuranoside; As-Oxide
C10H21AsO7
Biological Source
Biological Use
Constit. of brown algae Dictyota pardarlis, f. pseudohamata A7749 and Dictyota divaricate Occurs in brown algae Fucus vesiculosus, Fucus spiralis, Pelvetia canaliculata, Laminaria cloustoni, and Desmarestia aculeata Isol. from red algae Alsidium, Chondria, Laurencia, Polysiphonia, Halopytis, Vidalia, and Digenea spp. Isol. from brown algae Laminaria japonica and Ecklonia radiata, giant clam Tridacna maxima and various freshwater mussels Anodonta anatina, Dreissena polymorpha, Unio pictorum and Unio tumidas
Antimalarial agent
Structure
References [253]
HO
O
O
[254]
[255]
HO
OH
[256] O
O
HO OH
As O
CHAPTER 6 Algae-Based Biologically Active Compounds
3,4:7,8-Diepoxy-12dolabellen-18-ol; (1R*,3R*,4S*,7R*,8R*,11R*)form
Molecular Formula
212
Sr. No.
11
5,6-Epoxy-5,6-dihydro-b,εcarotene-3,30 -diol
C40H56O3
12
11,12-Epoxy-10-hydroxy5,8,14-eicosatrienoic acid; (5Z,8Z,10S,11S,12S,14Z)form
C20H32O4
13
Flexixanthin; 20 -Hydroxy, 20 O-a-L-rhamnopyranoside
C46H64O8
14
Fucoxanthinol; 30 -Ac
C42H58O6
3-O-a-D-Galactopyranosyl-
C12H22O11
D-galactose
16
C9H18O8
Constit. of various marine red algae
Insulin release enhancer; active against grampositive bacteria; toxic to brine shrimp
[257]
O O
OH
HO
[258]
Antioxidant, antifouling agent
[136,259]
O O
OH HO O
O
[260,261]
HO HO
[205,262] HO O
213
1-OGalactopyranosylglycerol; a-D-(2R)-form
[251]
6.6 Therapeutic Applications of Algae
15
Isol. from a variety of higher plants and from algae Constit. of Murrayella periclados, and algae Platysiphonia miniata and Cottoniella filamentosa Isol. from bluegreen algae Oscillatoria limosa and Phormidium faveolarum Constit. of algae, Fucus virsoides, Polysiphonia nigrescens, Colpomenia peregrina, Phaeodactylum tricornutum, Ceramium rubrum, and Hijikia fusiformis Isol. from Aeodes ulvoidea and Pachymenia carnosa
OH O
HO OH
Continued
214
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algaedcont’d
17
18
Name 2-O-a-DGalactopyranosylglycerol
Mannuronic acid: D-form
Molecular Formula C9H18O8
C6H10O7
Biological Source Constit. of many red algae, such as Plocamium cartilagineum, Laurencia pinnatifida, Iridaea laminaroides, and Bacillus coagulans Macrocystis pyrifera
Biological Use The main reserve carbohydrate in most red algae; prob. intracellular osmotic regulator
Structure
[205,263]
HO
O
HO
O OH
HO OH
O
HO
OH
HO
O OH
OH
HO
O O HO
HO HO
1,3,6-Tribromo-8methoxydibenzofuran
C13H7Br3O2
Isol. from crustose coralline red algae
1-O-D-Glucopyranosyl-Dmannitol; b-form
C12H24O11
HO
OH
Stypoldione
C27H38O4
Constit. of algae Stypopodium zonale, Stypopodium flabelliforme, and mollusk Aplysia dactyomela
Ichtyotoxin, algicide, toxic to sea urchin eggs; phospholipase A-2 inhibitor, microtubule inhibitor
O OH
[126] Br
O OH
OH HO HO
21
OH
Br
O
Constit. of F. vesiculosus and other brown algae
O
OH
Br
20
[264]
OH
HO
HO
19
References
HO
[265]
OH O O
OH
OH
[266]
HO
O
O O
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
b-D-Xylopyranosyl-(1/3)b-D-xylopyranosyl-(1/3)-Dxylose;
C15H26O13
23
Myxol; 20 -O-6-Deoxy-a-Lglucoside
C46H66O7
24
Neoxanthin; (all-E)-form
C40H56O4
25
Violaxanthin; (all-E)-form
C40H56O4
26
Glycerol 1,2-dialkanoates; glycerol 1,2-dioctanoate, 3O-(6-Deoxy-6-sulfo-a-Dglucopyranoside)
C41H78O12S
Constit. of the Penicillus dumetosus, Rhodymenia palmate, and several other green algae Isol. from Oscillatoria rubescens, Oscillatoria agardhii, Arthrospira spp., and Phormidium luridum Constit. of paprika, lucerne, maple, Valencia orange; also in green algae
[267]
Constit. of many plants including V. tricolor; found in brown and green algae Constit. of the Byrsonima crassifolia and the algae Gracilaria verrucosa and Sargassum parvivesiculosum
[269]
[109,268]
6.6 Therapeutic Applications of Algae
22
[269]
[270]
215
Continued
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algaedcont’d
27
Violaxanthin; (all-E)-form, Monodeoxy
Chitin
Molecular Formula C40H56O3
C8H13NO5
Biological Source Isol. from the algae of Xanthophyceae, Eriobotrya japonica, and Prunus persica Occurs in crustacea, most fungi, mycelial yeast, green algae, and some brown and red algae
Biological Use
Structure
References OH O
O
Antihemorrhagic; used as a wound healant
H2 P O H N
O
HO
[271] O
O
OH O
HN
2,3-Dihydroxypropyl [5deoxy-5-(dimethylarsino)] ribofuranoside; As-Oxide, O30 -sulfate
C10H21AsO10S
30
5-Methyl-2furancarboxaldehyde
C6H6O2
31
a,a-Trehalose
C12H22O11
Isol. from T. maxima and brown algae Sargassum lacerifolium and Hizikia fusiforme Isol. from brown algae and other plant sources Occurs in fungi, molds, ergot, algae, yeast, and many insects
OH
OH
O
29
[269]
PH2
OH O O HO S
O
[272]
O
O
As
HO
Flavoring ingredient
Probable energy reserve in many organisms and important cellular protectant in drought resistant organisms; associated with maintenance of the integrity of biological membranes in organisms subject to severe thermal stresses; marker for tubercuosis infection in vivo
OH
O
O
[273]
OH HO
[274]
OH O
OH
HO
O O OH
HO OH
O
CHAPTER 6 Algae-Based Biologically Active Compounds
28
Name
216
Sr. No.
Galactose; L-form
C6H12O6
Occurs in agar eagar, chagual gum, red algae, flax seed mucilage, and a snail galactan
33
Mannose; D-form
C6H12O6
Phytelephas macrocarpa, Orchidaceae, Phoenix canariensis, Amorphophallus konjac; they are proliferated by some red algae and yeasts; also occurs in trace amounts in apples and peaches
Constit., constituents; Isol., isolated.
[275]
Inexpensive starting material for chiral synthesis
[275]
6.6 Therapeutic Applications of Algae
32
217
218
Sr. No. 1
2
3
Name Erythritol
Molecular Formula C4H10O4
2-Methyl-1,2,3,4butanetetrol; (2R,3R)-form, 4phosphate
C5H13O7P
1-Deoxy-1(dimethylarsinoyl) ribitol; 5-O-sulfate
C7H17AsO8S
Biological Source Found in a variety of algae, lichens and fungi; produced by Protococcus vulgaris, Trentepohlia iolithus, and Aspergillus terreus Bacteria, algae, and plant chloroplasts
Biological Use Bulk sweetener with good taste props; also thickener, stabilizer, humectant, etc. in food, shows vasodilatory props The first pathway-specific intermediate in the methylerythritol phosphate route for biosynthesis of isoprenoid compounds in bacteria, algae, and plant chloroplasts
Structure
References
OH
[276]
OH OH
O HO
OH
[277]
O P OH
OH
HO OH
O As
Isol. from Chondria crassicaulis and other red algae
HO
[278]
OH
HO O
S O O OH
4
5
Talitol; D-form
Mannitol; D-form
C6H14O6
C6H14O6
Isol. from various brown algae including Himanthalia elongata and Notheia anomala Olive and plane trees; obtained from manna and seaweeds; obtained industrially from fructose
OH
HO
Energy reserve in brown algae Diagnostic aid (renal function determination); diuretic; tablet and capsule diluent
[279,280]
OH
HO
OH HO
OH OH
HO HO
OH HO
[276]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.13 Alcohols: Biologically Active Constituents Extracted From Algae
6
1,1,3,3Tetrabromo-2heptanol
C7H12Br4O
7
2-Nonen-1-ol
C9H18O
8
Glucitol; D-form
C6H14O6
10
1-Bromo-3-iodo2-propanol; (x)form D-glycero-Dmanno-heptitol
[222]
Br
Br
OH Br
Present in melon, cucumber, brown algae, nectarine, and prickly pear Present in algae, apples, pears, cherries, and apricots; also present in Sorbus and Crataegus spp.
C3H6BrIO
Present in red algae Asparagopsis taxiformis
C7H16O7
Occurs in mushroom Lactarius volemus, in primulae and in Escherichia coli; also in red algae
Constit., constituents; Isol., isolated.
Used in food flavoring
Used in manufacture of sorbose, propylene glycol, ascorbic acid, resins, plasticizers and as antifreeze mixtures with glycerol or glycol; tablet diluent, sweetening agent and humectant, other food uses; used in photometric detn. of Ru(VI) and Ru(VIII); in acid ebase titration of borate
OH
OH OH
HO HO
[281]
[280]
OH HO
Br
[282]
I OH
OH
[276]
OH OH
HO
HO
OH HO
6.6 Therapeutic Applications of Algae
9
Br
Constit. of red algae Bonnemaisonia spp.
219
220
Sr. No. 1
2
3
4
Name 1,2-Diacylglyceryl-3-(Ocarboxyhydroxymethyl) choline 1,2-Diacylglyceryl-O-20 (hydroxymethyl)-N,N,Ntrimethyl-b-alanine Ulvaline
Lactyltrimethylarsonium betaine
Isol., isolated.
Molecular Formula
Biological Source
Biological Use
Betaine lipid present in some plants and algae
Structure
HO
O
O
O
O
References -
[283] N
+
OH
Isol. from various marine algae C10H21NO5
C6H13AsO3
Isol. from the marine plant Monostroma nitidum and the mushroom Lampteromyces japonicus; isol. from numerous marine sources including algae and bryophytes Marine algae, e.g., Dunaliella tertiolecta; also in diatom Chaetoceros concavicornis and lobster Homarus americanus
HO
O OH
Shows hypocholesterolaemic activity
-
O
[283]
O
[284]
O
+
N
OH O
O
N O
O
HO As
OH
[285]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.14 Lipids: Biologically Active Constituents Extracted From Algae
Table 6.15 Carbonyl Compounds: Biologically Active Constituents Extracted From Algae Sr. No.
Name
Molecular Formula
Biological Source
1
1,1-Dibromo-3-iodo2-propanone
C3H3Br2IO
Red algae, Asparagopsis taxiformis, and Asparagopsis armata
2
1,3-Dibromo-2propanone
C3H4Br2O
3
8,11,14Heptadecatrienal; (allZ)-form
C17H28O
4
1-Bromo-2propanone Dibromoacetaldehyde
C3H5BrO
Constit. of the marine algae A. armata, A. taxiformis, and Falkenbergia rufolanosa Constit. of cucumber, tobacco, and wheat; also found in the algae Enteromorpha sp., Scytosiphon lomentaria, and Ulva pertusa Isol. from the algae A. taxiformis and F. rufolanosa Isol. from the algae A. taxiformis and F. rufolanosa Component of red algae A. taxiformis, A. armata, and tetrasporophyte F. rufolanosa Constit. of seaweed Dictyopteris plagiogramma, green algae Bryopsis pennata, Caulerpa prolifera, and Cymopolia barbata, and other marine algae
Biological Use
Structure
References
O Br
[234]
I Br
6
7
1,3-Dibromo-1-chloro2-propanone; (0004)-form 3-Hexyl-1,2-dithiepan5-one; (0003)-form
C2H2Br2O C3H3Br2ClO
C11H20OS2
Br
[234] Br
O
Br
O
[286,287]
O
[234]
Br
[234]
Br O
[234]
Br Br
Cl
[288] S S O
Continued
6.6 Therapeutic Applications of Algae
5
O
221
222
Sr. No.
Name
Molecular Formula
Biological Source
8
2-Tridecyl-2heptadecenal; (E)-form
C30H58O
Constit. of red algae Corallina mediterranea, Laurencia obtusa, Laurencia papillosa, and Laurencia undulata; also prod. by a marinederived Cladosporium sp.
9
1,1,3-Tribromo-3chloro-2-propanone
C3H2Br3ClO
Red algae A. taxiformis and F. rufolanosa
10
1,1,3-Tribromo-2propanone
C3H3Br3O
Constit. of red algae Asparagopsis spp. and F. rufolanosa
11
6,10,14-Trimethyl-2pentadecanone; (x)form
C18H36O
Present in marine organisms such as sponge Spheciospongia vagabunda, algae Caulerpa taxifolia, and Padina tetrastromatica, and crab Carcinus maenas
Biological Use
Structure
[289]
O Br
[234]
Br Br
Constit., constituents; Isol., isolated.
References
Cl
O
[234]
Br Br
Br O
[290]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.15 Carbonyl Compounds: Biologically Active Constituents Extracted From Algaedcont’d
Table 6.16 Other Compounds Extracted From Algae Sr. No. 1
Name 2-Amino-6-(1,2-dihydroxypropyl)4(1H)-pteridinone; (10 R,20 R)-form
Molecular Formula
Biological Source
C9H11N5O3
Widely distributed in microorganisms, insects, algae, amphibian, and mammals; Found in urine Found in algae, lobsters, sharks, and dogfish
Growth factor
Appears to be a hormonal messenger involved in cyclic GMP regulation; vasodilator. Used in the prophylaxis of graft dysfunction in patients receiving allogenic kidney transplants Selective reducing agent; reagent for ortho-alkylation of aromatic amines; used with diborane as effective reducing agent for esters, amides, etc.
Arsenobetaine
C5H11AsO2
3
Carbon monoxide
CO
Produced in traces by algae and higher plants
4
Dimethyl sulfide
C 2H 6S
Isol. from green and red algae and higher plants
Structure
[291]
OH
HO
References
N N
O N
NH NH2
[292]
-
O+
C
S
[293]
6.6 Therapeutic Applications of Algae
2
Biological Use
[294]
Continued
223
224
Sr. No. 5
Name 1-Pentacosene4,6,8,10,12,14,16,18,20-nonol; (4S,6S,8S,10S,1214R,16R,18R)form, Nona-Me ether
Molecular Formula
Biological Source
C34H68O9
Isol. from the bluegreen algae Scytonema burmanicum and Scytonema mirabile
Biological Use
Structure
References [114]
O O O O O O O O O
6
3-(Dimethylarsinyl)propanoic acid
Isol., isolated.
C5H11AsO3
Found in lobster, dogfish, oyster, blue mussel, horse mussel, scallop, cod, brown algae Ascophyllum nodosum, and Fucus vesiculosus
O
[295]
As
OH
O
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.16 Other Compounds Extracted From Algaedcont’d
6.6 Therapeutic Applications of Algae
some of which are characterized as proteoglycans [296]. Thrombin and plasmin are the proteolytic enzymes required for the activation of enzymes in fibrinolytic and coagulation cascade (Fig. 6.1). The balance between both pathways is obligatory, otherwise strokes and heart attacks are obvious due to excessive bleeding or thrombosis. Deep vein thrombosis is the major cause of mortality in posttraumatic cases and promulgates in operated patients [298]. Anticoagulant therapy is very beneficial in such situations. The first report of algal polysaccharide as anticoagulant agent was published in 1936 when Chargaff and colleagues succeeded to isolate the esters of sulfuric acid and galactan from Iridae laminarioides having anticoagulant activity equal to 30 U/mg of heparin. Consequent analysis revealed carrageenan and agar having similar anticoagulant properties. Up till now, approximately 150 species belonging to red-brown, green, and microalgae have been used to isolate this heterogeneous sulfated biopolymer (Table 6.17). Sulfated biopolymer heparin has been used as an anticoagulant since past 50 years in posttraumatic patients [317]. Its anticoagulating effect is expressed by heparin cofactor-II and antithrombin potentiation, a major anticoagulating enzyme (Fig. 6.1). However, algal-sulfated polysaccharides are most extensively studied as anticoagulants, more extensive studies are needed to overcome side effects, i.e., thrombocytopenia. [297]. This side effect was overcome by synthesizing low molecular weight algal-sulfated polysaccharides [318]. Similar to the algal-sulfated polysaccharides (heparin), dermatan sulfate, in combination with chondroitin sulfate, is also clinically employed, but unfortunately is little potent due to its high molecular weight [27]. Fucoidan from Ecklonia kurome is found to be more potent due to low molecular weight fractionation and low sulfation [319]. It was also observed that branched fucans isolated from brown algae have direct effect while linear fucans isolated from echinoderms require some antithrombin molecules for their action [320].
FIGURE 6.1 Schematic presentation of antithrombotic activity: antithrombotic effect of sulfated polysaccharides; (A) activation of prothrombin versus inactivation of prothrombinase by treating with sulfated polysaccharides [297].
225
226
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.17 Major Sugar Molecules of Algal Polysaccharides (PSs) Exhibiting Anticoagulating and Antithrombotic Agents Species
Major Sugar
PS
References
Grateloupia indica Gigartina skottsbergii Nothogenia fastigiata Lomentaria catenata Schizymenia binderi Porphyra haitanensis Monostroma nitidum Lessoni avadosa Ecklonia cava Ascophyllum nodosum Ecklonia kurome Monostroma latissimum Ulva conglobata Codium cylindricum Codium pugniformis Codium fragile Dictyota cervicornis Caulerpa cupresoides E. cava
Galactose Galactose Mannose Galactose Galactose Galactose Rhamnose Fucose Fucose Fucose Fucose Rhamnose Rhamnose Galactose Glucose Arabinose Mannose, fucose Galactose Arabinose, galactose
sPS sPS EsPS Galactan Galactan sPS PS (sulfated) PS (sulfated) PS (sulfated) PS (sulfated) PS (sulfated) sPS sPS Galactan sPS Arabinans Rhamnose Galactan Aribanogalactan
[299] [300] [301] [302] [303] [304] [305] [306] [307] [308] [309] [310] [311] [312] [302] [313] [314] [315] [316]
6.6.2 ANTIVIRAL ACTIVITIES OF ALGAE-BASED BIOLOGICALLY ACTIVE COMPOUNDS The use of algal polysaccharides as antiviral agent is not new as it goes back more than 50 years when Gerber and his colleagues inhibited influenza-B virus and mumps in 1955 [321]. Later it was assumed that the antiviral effect of sulfated polysaccharides was due to electrostatic prevention of viral adherence to cell surface [322]. This gushed exploration of antiviral achievements of diverse-natured sulfated polysaccharides including polyanionic substances [323]. With the structural elucidation of algal polysaccharides, isolation of seaweed polysaccharides as antiviral agents was substantially increased due to their ability to affect the viral replication by a number of nonspecific mechanisms (Fig. 6.2) [324]. Cladosiphon okamuranus fucan inhibited DENV-2 (Dengue fever type-2) with BHK-21 cells, but had very little effect on other serotypes. Structural analysis of DENV-2 enveloped glycoprotein exhibits that arginine-323 close to heparin-binding site is censorious for fucan interaction [27]. In accordance with these findings, Talarico and colleagues published that sulfated biopolymer from two genera of red algae, i.e., carrageenan from Gymnogongrus griffithsiae and galactan from Cryptonemia crenulata completely impeded DENV-2, with less impedance on DENV-3 and DENV-4, while
6.6 Therapeutic Applications of Algae
FIGURE 6.2 Antiviral mode of action of sulfated polysaccharides: antiviral mode of action of sulfated polysaccharides [297]; (A) binding of pathogen with host cell; (B) neutralization of pathogen.
remained ineffective against DENV-1 in cell lines [325,326]. These biopolymers use the phenomenon of adsorption, only when added soon after infection, as no inhibition was observed when viral entry was avoided by transfection into the cells [327]. Inhibition of herpes simplex virus-1 and -2 (HSV-1, HSV-2) by sulfated biopolymers has become a hot issue these days [328,329]. Sulfated xylomannan of Sebdenia polydactyla exhibited high potency against HSV-1 due to high sulfation, and the potency is further increased by increasing sulfation [330]. Inhibition of different viral species (Table 6.18) by biopolymers of different algal species indicated that Table 6.18 Effect of Algal Sulfated Polysaccharides (PSs) on Different Virus Species Species
Virus Strain
EC50/ED50 (mg/mL)
Type of PS
References
Schizymenia pacifica Nothogenia Fastigiata Digenea simplex Pterocladia capillacea
HIV-1
7e14
Carrageenan
[331]
HIV-1
061e1.35
(Xylo)mannans
[332]
HIV
2.84
[333]
HSV-1
2.6e10
Gigartina skottsbergii Cryptopleura ramosa Salvia interrupta
HSV-1, HSV-2
>1
sp. noncharacterized Sulfated agarans and hybrid DLgalactans Carrageenan
HSV-1, HSV-2
1.6e4.2
[335]
HSV-1, HSV-2
1.5e36
Sulfated agarans Carrageenans
[334]
[335]
[329] Continued
227
228
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.18 Effect of Algal Sulfated Polysaccharides (PSs) on Different Virus Speciesdcont’d Species
Virus Strain
EC50/ED50 (mg/mL)
Type of PS
References
Sulfated agarans Sulfated agarans
[336]
1 and 0.7 e6.6 Asparagopsis armata Porphyridium cruentum
Gyrodinium impudicum Rhodella reticulata
Monostroma latissinum Porphyridium sp.
HIV
40.2
African swine fever virus (ASFV); vaccinia virus (VACV); vesicular stomatitis virus (VSV) Encephalomyocarditis virus; influenza A virus (Flu-A) HSV-2; varicela zoster virus (VZV); murine sarcoma virus (MuSV124), and MuSV/ MuLV (murine eukemia virus) HSV-1, HCMV, HIV-1
12e56; 20e45
0.19e0.48
Hybrid DLgalactans
[309]
10e20; 8; 150 and 50
Sulfated agarans
[337]
3.7
Sulfated Rhamnans Extract
[338]
Extract
[340]
Fucans
[341]
0.5e1.9
Fucans
[338]
HSV-1, HCMV HIV-1
45.5
Fucans
[342]
HIV-1
49
Fucans
[302]
HSV-1, HSV-2
Cochlodinium polykrikoides
HIV-1, RSV, Inf A, Inf B
Pennisetum purpureum
Vaccinia virus VACV and VACV-GFP; ectromelia virus (ECTV) HSV-1
Leathesia difformis Sargassum horneri Fucus vesiculosus
[242]
1e5 (in vivo, 100); 0.7; 10 and 5 (RT50) 0.45e1.1 and 7.1e8.3; 2.0e3.0 and 0.8; 1.7; 4.52e21.6; 0.8e25.3 0.65
[339]
6.6 Therapeutic Applications of Algae
antiviral activity is greatly affected by degree of sulfation, arrangement of sulfate, composition of sugar moieties, stereochemistry, or its molecular weight [343]. HSV-2 is inactivated by direct incubation with sulfated biopolymer as in vivo consequence of virucidal activity is related with amplification of antiviral activity [335].
6.6.3 ANTIOXIDANT ACTIVITY Free radicals are highly reactive molecules with an unpaired electron and are produced by radiation or as by-products of metabolic processes. They initiate chain reactions which lead to disintegration of cell membranes and cell compounds, including lipids, proteins, and nucleic acids [327]. Antioxidant compounds scavenge free radicals such as peroxides and reduce the level of oxidative stress and slow/prevent the development of complications associated with oxidative stresserelated diseases [344]. The use of algal biopolymers was totally ignored as an antioxidant agent but the recent studies revealed that algal compounds have considerable antioxidant competence [345]. As being photoautotrophs, micro/macroalgae possess a trenchant, antioxidant magpie complex for their self-defense against radical and oxidative stresses [346]. ROS (reactive oxygen species), i.e., superoxide anion, hydrogen peroxide, and hydroxyl radicals, dissimulate pharmaceutical security and diminish food quality by oxidation of lipids. Algal-sulfated biopolymers not only act as dietary fibers but also act as free-radical scavengers (Fig. 6.3), e.g., Tannin et al. [347] reported that Porphyridium spp. prevented autooxidation of linoleic acid and repressed oxidative damage to 3T3 cells caused by FeSO4. Their further studies revealed that the antioxidant activity was dose dependent having positive correlation with sulfur contents conferring free-radical scavenger activity. Carrageenans and
FIGURE 6.3 Antioxidant Activity of Algal Extract. : Inhibition by algal extract. A step at which algal extracts prevents the tissue damage by inhibiting lipid peroxidation, superoxide, peroxide, hydroxyl ions formation.
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ulvans bioactivities were found to be correlated with the contents of sulfate [348]. Fractions of fucan from Laminaria japonica and Fucus vesiculosus exhibited positive correlation between fucose and sulfate concentration to act as metal chelator and free-radical and insulin-dependent scavenger [349]. Sun et al. [350] reported that low molecular weight fractions (6.55 kDa) of sulfated biopolymers isolated from Porphyridium cruentum exhibited higher antioxidant activity against ascorbic acid than FeSO4-induced peroxides having high molecular weight (256 kDa) in mouse cells. Scientists reported that sulfated biopolymers of Arthrospira were stronger superoxide anion radical scavenger than a-tocopherol. Crude extract was two times stronger than a-tocopherol. Seaweeds also reported recognized antioxidants such as terpenoids [351], carotenoids, mycosporine-like amino acids, phlorotannins, ascorbic acid, tocopherols [352], and algal-sulfated polysaccharides [353]. Laminaria digitata and Himanthalia elongata have been reported to exhibit antioxidant activity comparable with those of vitamin E and butylhydroxyl toluene (BHT) [347]. Antioxidant activity was also reported from Sargassum micracanthum [354], Rhodomela confervoides, Symphocladia latiuscula [355], Kappaphycus alvarezzi [356,357], Gelidiella acerosa [358], F. vesiculosus [359], diphlorethohydroxycarmalol and 6,60 -bieckol isolated from Ishige okamurae [360], Undaria pinnatifida [361], ethanolic extract of Sargassum pallidum [362], Enteromorpha compressa, Capsosiphon fulvescens [363], Halimeda incrassate [364], Eisenia bicyclis, Kjellmaniella crassifolia, Alaria crassifolia, Sargassum horneri, and Cystoseira hakodatensis [365]. Fucoidan derivatives, oversulphated, acetylated, and benzoylated fucoidan isolated from L. japonica, show potential antioxidant activity in vitro [345,353]. In vitro antioxidant activity of iota, kappa, and lambda carrageenans, homofucan from the edible seaweed F. vesiculosus, and heterofucans from the seaweed Padina gymnospora were also reported [366]. Astaxanthin, an antioxidant obtained from Haematococcus pluvialis is marketed [348].
6.6.4 ANTICANCER ACTIVITY Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells. If the spread is not controlled (Fig. 6.4), it results in death. Isolation of cytotoxic antitumor substances from marine organisms was reported in several references during the last 40 years, while in recent years, hundreds of potential antitumor agents were isolated from marine origin especially from marine algae [367]. Biological properties of seaweeds such as reduction of plasma cholesterol, binding of biliary steroids, inhibition of carcinogenic fecal flora, binding of pollutants, stimulation of the immune system, and the protective effects of b-sitosterols seaweed suggested them as a potent therapeutic agent against breast cancer. The low rate of breast cancer in Japan is associated with high seaweeds consumption [368]. Certain algae have long been used in traditional Chinese herbal medicines for the treatment of cancer [369]. Sulfated polysaccharides, including fucoidans and carrageenans, inhibit tumor metastasis in rats by inhibiting the action of the tumor cellederived heparanases
6.6 Therapeutic Applications of Algae
FIGURE 6.4 Anticancer Mode of Action of Algal Extract. : Inhibition by algal extract. Algal polysaccharides inhibit the proliferation of various types of cancer and cell cycle arrest at G0/G1 S or G2/M phase. Apaf-1, apoptotic protease activator factor; Bax, Bcl-2-like protein; Bcl2, B-cell lymphoma2; P53, tumor protein.
involved in membrane crossing [370e372]. Carrageenan from Sargassum kjellmanianam [373] significantly inhibited S-180 and leukemia-1210 ascites tumor growth effect of mitomycin in mice [374]. Carrageenan from rodophyta was also found to stimulate lectin-dependent, cell-mediated cytotoxicity against HEp-2 human epipharynx carcinoma cells [375]. Various brown algae, namely Scytosiphon lomentaria, Lessonia nigrescens, L. japonica, Sargassum ringgoldianum, red algae, Porphyra yezoensis and Eucheuma gelatinae, and the green alga, Enteromorpha prolifera have shown antitumor activity against Meth-A fibrosarcoma [376]. Fucoidans isolated from brown seaweed Sargassum thunbergii have proven antitumor activity [377,378]. Ulvan extracted from Ulva lactuca has shown cytotoxicity against human colon cell line [29]. Facosterols isolated from Turbinaria conoides also displayed cytotoxicity against human (HU) cell lines [379]. Caulerpenyne isolated from Caulerpa taxifolia exhibited antitumor activity against HU neuroblastoma cell line by inhibiting microtubule assembly and tubulin aggregation [380]. Compounds of dihydroxysargaquinone and sargatriol from Sargassum tortile [381] and diterpene from Sargassum crispum are known for their cytotoxic activities [382].
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Cytotoxicity of fucodian extracted from Sargassum swartzii and Sargassum denticaprum against some human cancer cell lines [383], antitumor activity of Gracilaria corticata against Jurkat and molt-4 human cancer cell lines [384], Spyridia filamentosa against human prostate carcinoma epithelium-like cell lines DU-145 [385], S. swartzii, Cystoseira myrica, and Colpomenia sinuosa against Colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), tamoxifen-resistant breast ductal carcinoma (T47D-T.R), and estrogenindependent breast carcinoma (MDAMB468) cell lines [386], Arthrospira platensis, Dunaliella salina and Aphanizomenon flosaquae, and H. pluvialis against the growth of human leukemia cell line HL-60, and the biphenotypic B myelomonocytic leukemia cell line MV-4-11 [387] were reported.
6.6.5 ANTIINFLAMMATORY ACTIVITY Algal-sulfated biopolymers are potent immunomodulators with the ability to control the activity of immune cell activity and to stimulate the immune response [388]. Algal cell wall polysaccharides jolt an outcome and progression of disease by complex targets [24]. Intravenous injection of fucoidan reduced leukocyte rolling in meningitis and similarly also reduced leukocyte enlisting to peritoneum [389]. Commercially available (SigmaeAldrich Chemical Co.) fucoidan from F. vesiculosus exhibits antiinflammatory activity by inhibiting the cell adhesion process by binding with P- and L-selectins. Fucans from Fucus spp. C. okamuranus, Ascophyllum nodosum, and Laminaria spp. treat rats’ acute peritonitis by inhibiting leukocyte recruitment toward abdominal cavity [390]. In addition to impairment of selection actions, these sulfated biopolymers have the ability to completely inhibit elastase and heparanase responsible for degradation of membrane integrity (Fig. 6.5). It was reported that sulfated biopolymers had the ability to inhibit the complement activation by binding with C-4, anticipate schism product required for the synthesis of C-3 convertase [391]. Tissot and colleagues [392] succeeded to isolate low molecular weight fractions of fucoidan that have shown their ability to inhibit the complement by binding with immune complexes and also influence the C-1q and activate C-1 to recognize IgG. Structural elucidations using NMR revealed that branched fucoidan oligosaccharides are more potent than linear structures for inhibition of complement system [393,394]. Fucoidan influencing the complement system, also affect innate immunity rendering the pro-inflammatory state by reducing allergic reactions. Furthermore, it was also observed that sulfated algal cell wall polysaccharides also regulate innate immunity by binding with phagocytes and macrophages [395]. lcarrageenan generates cytokine response by stimulation of T-cell cultures in a TLR4 (toll-like receptor-4) in mice [396]. However, TLR4-deficient splenocyte mice also produced g-interferon after injection of l-carrageenan indicating that PRRs (proline-rich polypeptides), in addition to TLR4, were also provoked. It was reported that l-carrageenan might be applied to amend allergic reactions. U. pinnatifida fucoidan expressed similar results [397] in accordance with the
(A) Untreated inflammation; (B) treated inflammtion with sulfated polysaccharides [297].
6.6 Therapeutic Applications of Algae
FIGURE 6.5 Antiinflammatory Role of Sulfated Polysaccharides.
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findings of Tsuji et al. [396]. Reduction in inflammation is due to its interaction with other factors such as inducible nitric oxide synthase (iNOS) and cytokines, e.g., fucoidan isolated from F. vesiculosus incurred NO by attracting macrophages, causing the reduction in inflammation beyond impairment of LPS (lipopolysaccharide) [398]. Desulfation of sulfated polysaccharides from Ulva rigida is associated with complete attenuation of immunostimulatory activity [309]. Moreover, sulfated biopolymers from various species of algae, i.e., Phaeodactylum, Chlorella stigmatophora, and Porphyridium, were found to be effective antiinflammatory agents. Raposo et al. [399] reported that carrageenans and fucoidans aggravated the cytotoxicity of macrophages, lymphocytes, and natural-killer cells opposed to tumors. The antiinflammatory effect of Sagarssum hemiphyllum against Phorbol 12-myristate 13acetate (PMA) and A23187-induced interleukin-8 (IL-8) and on tumor necrosis factorea (TNF-a) secretion from human mast cells (HMC-1) [400], Galaxaura marginata against Croton oil induced mouse ear edema [401], S. thunbergii and Sargassum fulvellum against phorbol myristate acetate-induced ear edema, erythema, and blood flow [402], Porphyra dentata against LPS-induced RAW 264.7 macrophages [403], Petalonia binghamiae against ethyl acetate LPS-induced RAW 264.7 macrophages [404], S. swartzii and Ulva reticulata against Carrageenan-induce inflammation [405], Dichotomaria obtusata, against waterear edema induced by TPA and writhing-induced hind paw edema in rats and peritonitis for acute and chronic inflammatory mode by acetic acid [406], and T. conoides against carrageenan-induced hind paw edema [407] were also reported. On the basis of these reports, sulfated biopolymers can be used for therapeutic purposes in allergy and autoimmune diseases.
6.6.6 ANTIULCER ACTIVITY Chromene compound extracted from the seaweed S. micracanthum is reported to possess antiulcer property [408]. Methanolic extract of red algae Gracilaria changii shows antiulcer activity [409]. It is also exhibited by seaweeds Turbinaria ornata, Gracillaria crassa, and Laurencia papillosa [410].
6.6.7 ANTIDIABETIC ACTIVITY Diabetes is one of the most serious, chronic diseases that is developing with the increase in obesity and aging in the general population. It is largely classified into insulin-dependent diabetes mellitus (type-1 diabetes) and non-insulin-dependent diabetes mellitus (type-2 diabetes) [411e413]. Phlorotannins derived from brown algae exhibited their various antidiabetic mechanisms such as a-glucosidase and a-amylase inhibitory effects (Fig. 6.6). Dieckol, Fucodiphloroethol G, 6,60 -Bieckol, 7-Phloroeckol, Phlorofucofuroeckol-A isolated from Ecklonia cava; Phloroglucinol, Eckol, and Dioxinodehydroeckol isolated from Ecklonia Stolonifera and Ecklonia bicyclis; and Octaphlorethol-A isolated from Ishige foliacea show antidiabetic
6.6 Therapeutic Applications of Algae
FIGURE 6.6 Schematic Presentation of Antioxidant Activity of Algal Extracts. : Inhibition by algal extract. Algal extracts prevents from diabetic complications by inhibiting the production of sorbitol, free radicals, and oxidative stress expressed by cross sign.
effects [395]. Octaphlorethol-A (OPA), a type of phlorotannin isolated from Ishige foliacea, is shown to have antidiabetic activities [414]. Diphlorethohydroxycarmalol (DPHC) isolated from I. okamurae is a potent inhibitor for a-glucosidase and a-amylase [415]. Seaweed lipids also show antidiabetic activity [416].
6.6.8 ANTITHROMBIN ACTIVITY Strong antithrombin or antithrombotic activity is exhibited by fucoidans isolated from Laminaria saccharina, L. digitata, Fucus serratus, Fucus distichus, and Fucus evanescens [390]. A novel sulfated galactofucan isolated from Spatoglossum schroederi showed potent antithrombotic activity [417]. A fucan sulfate isolated from E. kurome [418] and S. schroederi exhibited antithrombic activity [419]. A bromophenol derivative named (þ)-3-(2,3-dibromo-4,5-dihydroxy-phenyl)-4-bromo-5,6dihydroxy-1,3-dihydroiso-benzofuran, isolated from brown alga Leathesia nana, also exhibited good in vivo antithrombotic activity [420].
6.6.9 ANTIOBESITY ACTIVITY Obesity is a medical condition of excess body fat accumulation that impairs health. It is a major health problem throughout the world and an issue of growing concern in the 21st century. According to the World Health Organization, overweight and
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obesity are the fifth leading risk for global death, and at least 2.8 million adults die each year as a result of being overweight or obese. It is associated with the development of metabolic diseases such as type-2 diabetes as well as cardiovascular disorders, some types of cancer, and osteoarthritis [421]. Obesity is controlled by controlling appetite, blocking fat absorption, stimulating energy expenditure, suppressing adipose tissue growth, and by increasing body fat mobilization. Algal polysaccharides chitin and chitosan isolated from green algae, and alginate and fucoidan from brown algae show potential for weight loss with different mechanisms. Antiobesity effect of phlorotannins 7-phloroeckol, fucofuroeckol-A and eckol isolated from Ei. bicyclis and E. cava; carotenoids fucoxanthin from Ei. bicyclis and U. pinnatifida; astaxanthin isolated from H. pluvialis have also been reported [422]. Green algae carotenoid siphonaxanthin shows potent antifat activity [423].
6.6.10 ANTIANGIOGENIC ACTIVITY Angiogenesis results in new blood vessel formation from a preexisting vasculature that occurs under either physiological or pathological conditions [424]. In pathological conditions, such as inflammatory diseases, rheumatoid arthritis, and tumor metastasis, a chronic, unregulated angiogenic state often helps spreading of the diseases (Fig. 6.7). Hence preventing angiogenesis under pathological conditions is a promising approach in the prevention of cancer and other angiogenic-related diseases [425]. Algal carotenoid fucoxanthin effectively suppressed the differentiation of endothelial progenitor cells into endothelial cells involving new blood vessel formation (Fig. 6.7). Fucoxanthin and fucoxanthinol suppressed microvessel outgrowth in vivo and ex vivo angiogenesis assay using a rat aortic ring [426]. Antiangiogenic effect is also exhibited by siphonaxanthin derived from green algae Codium fragile [427].
6.6.11 HEPATOPROTECTIVE ACTIVITY Phloroglucinol and phloroglucinol derivatives eckstolonol, phlorofucofuroeckol-A (Fig. 6.8) isolated from the brown alga Ecklonia stolonifera exhibit hepatoprotective activity [428]. Hepatoprotective activities of carotenoids, b-carotene, and xanthophyll from microalgae, Spirulina platensis, and D. salina [429], and low molecular weight sulfated polysaccharide isolated from L. japonica were also reported [430]. Phloroglucinol protects liver damage due to oxidative stress produced by tributyl hydroperoxide (T-BHP), carbon tetra chloride, etc.
6.6.12 RADIOPROTECTIVE EFFECT Ionizing radiations are known to generate reactive oxygen species in irradiated tissue and cells. The primary damage caused by radiation is production of aqueous free radicals, generated by the action of radiation on water within the cell. These free radicals react with cellular macromolecules such as DNA, protein, and lipid membrane
6.6 Therapeutic Applications of Algae
FIGURE 6.7 Antiangiogenic Effect of Algal Derived Fucoxanthin. : Inhibition by algal extract. Algal extracts inhibits the synthesis of tumor by inhibiting the VEGF. EGF, epidermal growth factor; PDGF, platelet derived growth factor; VEGF, vascular endothelial growth factor.
causing cell dysfunction and mortality. Lungs are reported to be especially sensitive to oxidative stress. Eckol, a trimeric phloroglucinol with a dibenzeno-1,4-dioxin skeleton, one of the major phlorotannins isolated from brown alga E. cava is found to be a radioprorective agent. It acts by reducing the intracellular reactive oxygen species generated by g-ray radiation (Fig. 6.9). Moreover, eckol also protected against radiation-induced cellular DNA damage and membrane lipid peroxidation [431].
6.6.13 ANTI-ALZHEIMER ACTIVITY Alzheimer’s disease (AD) is an irreversible, progressive, neurodegenerative disorder of the central nervous system associated with progressive cognitive memory loss [432]. Neuropathological studies demonstrated that AD was associated with deficiency of the brain neurotransmitter acetylcholine (ACh). The inhibition of
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CHAPTER 6 Algae-Based Biologically Active Compounds
FIGURE 6.8 Hepatoprotective Effect of Algal Polymers. Phloroglucinol protects liver damage due to oxidative stress produced due to tributyl hydroperoxide (T-BHP), carbon tetra chloride, etc.
acetylcholinesterase (AChE) enzyme, which catalyzes the breakdown of ACh, can be one of the most realistic approaches to the symptomatic treatment of AD [433]. Methanolic extracts of marine algae Caulerpa racemosa, Codium capitatum, Ulva fasciata, Halimeda cuneata, Amphiora ephedraea, Amphiora bowerbankii, Dictyota humifusa [434], Hypnea valentiae, P. gymnospora, Ulva reticulate, and
FIGURE 6.9 Radioprotective Mode of Action of Phlorotannin. Phlorotannin from Ecklonia cava protects from radiation by activating immune system through increasing the levels of glutathione, oxidative enzymes, and free-radical scavengers whereas lowers apoptosis, mutation, and free-radical production.
6.6 Therapeutic Applications of Algae
Gracilaria edulis exhibit acetylcholinesterase inhibitory activity [435]. Fucosterol and 24-hydroperoxy 24-vinylcholestrol was isolated from n-hexane fraction of frozen Hypomecis formosana. Eckstolonol, eckol, phlorofucofluoroeckol0003A, dieckol, 2-phloroeckol, and 7-phloroeckol were isolated from the EtOAc extracts of Ecklonia stolonifera [436]. MeOH extracts and EtOAc extracts of I. okamurae exhibit inhibitory potential against AChE. 6,60 -bieckol isolated from I. okamurae serve as a potential AChE inhibitor that could be used as a potential functional food ingredient or nutraceuticals for preventing Alzheimer’s disease [437]. Sargaquinoic acid isolated from Sargassum sagamianum [438] and a glycoprotein from U. pinnatifida UPGP also exhibit acetylcholinesterase (AChE) inhibitory activity [439].
6.6.14 ACE INHIBITION ACTIVITY Increased blood pressure or hypertension is one of the major chronic medical condition, and one of the major independent risk factors for cardiovascular diseases. Angiotensin-I converting enzyme (ACE) plays a significant physiological role in regulating blood pressure by converting angiotensin-I to angiotensin-II, a potent vasoconstrictor. Therefore the inhibition of ACE activity is a major target in the prevention of hypertension (Fig. 6.10). The ethanol extract of E. cava, Ecklonia stolonifera, Phlorotannins such as eckol, phlorofucofuroeckol-A, and dieckol derived from E. stolonifera have shown considerable inhibitory activity against ACE [440]. Aqueous extracts of red algae Lomentaria catenata and Lithophyllum okamurae, methanolic extracts of Ahnfeltiopsis flabelliformis show inhibitory activity against ACE [441].
6.6.15 ANTITUBERCULOSIS ACTIVITY Antituberculosis activities of red algae Gelidium sp. were studied. Ether and alcoholic extracts of Gelidium amansii have shown a slight inhibition against M. tuberculosis while acetone extract of Gypsophila capillaris exhibited considerable inhibition toward Mycobacterium avium and Mycobacterium tuberculosis [442]. Diterpene, (1E,2R,3R,4S,6E,18S)-4,18-dihydroxydictyolactone isolated from the methanol extract of the brown alga Dictyota sp. exhibit weak antituberculosis activity [443]. Caulerpin a bis-indole alkaloid isolated from C. racemosa and Caulerpa serrulata exhibit excellent activity against M. tuberculosis. Biological results indicated that Caulerpin may be useful as a lead compound for the development of novel antituberculosis agents [444].
6.6.16 INSECTICIDAL ACTIVITY Polyhalogenated monoterpenes isolated from the red alga Plocamium cartilagineum exhibit insecticidal activity against the aster leafhopper [445]. Telfairine a monoterpene isolated from the red alga Plocamium telfairia shows strong insecticidal activity
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CHAPTER 6 Algae-Based Biologically Active Compounds
FIGURE 6.10 ACE (Angiotensin Converting Enzyme) Inhibition Role of Algal Extract. : Inhibition by algal extract. Algal extract acts on angiotensin converting enzyme. Algal extract inhibits the enzyme responsible (ACE and angiotensin-II) for hypertension and heart failure.
against the mosquito larvae Culex pipiens pallens [140]. Isodomic acids isolated from the red alga Chondria arnata show significant insecticidal activity when they are injected subcutaneously into the abdomen of American cockroach [446].
6.6.17 HYALURONIDASE-INHIBITION ACTIVITY Hyaluronidase is an enzyme that depolymerizes the polysaccharide hyaluronic acid in the extracellular matrix of connective tissue. The enzyme is known to be involved in allergic effects and migration of cancer and inflammation. Phlorotannins, phloroglucinol, such as eckol, phlorofucofuroeckol-A, dieckol, and 8,8-bieckol isolated from the brown algae Ei. bicyclis and E. kurome were reported to exhibit a stronger inhibition effect against hyaluronidase compared to well-known inhibitors such as catechin and sodium cromoglycate [447].
6.6 Therapeutic Applications of Algae
6.6.18 ANTIFUNGAL ACTIVITY A meroterpenoid isolated from the brown alga Cystoseira tamariscifolia, characterized as methoxybifurcarenone, possesses antifungal activity against three tomato pathogenic fungi [142]. Hexane extracts of three algal species Dictyota dichotoma, D. dichotoma var. implexa, and Dilophus spiralis exhibited a wide spectrum of antifungal activities having ability from process of cell membrane permeability to metabolic disruption (Fig. 6.11) which varied during the seasons [448]. Terpenoids isolated from algal species Stypopodium zonale, Laurencia dendroidea, A. nodosum, Sargassum muticum, Pelvetia canaliculata, Fucus spiralis, Sargassum filipendula, Sargassum stenophyllum, Laminaria hyperborea and G. edulis. S. zonale, L. dendroidea, P. canaliculata, S. muticum, A. nodosum, and F. spiralis possess antifungal activity; their extracts significantly inhibited the Colletotrichum lagenarium growth [449].
6.6.19 ANTIMALARIAL ACTIVITY Snyderol sesquiterpene derivative isolated from the red alga Laurencia obtusa was active against D6 and W2 clones of the malarial parasite Plasmodium falciparum [450]. Sphaerococcenol-A isolated from red alga Sphaerococcus coronpifolius is responsible for the antimalarial activity of the extract, against the chloroquineresistant P. falsciparum FCBI strains with an IC50 of 1 mM [451].
FIGURE 6.11 Antifungal Mode of Action of Algal Extract. : Inhibition by algal extract. Different steps at which algal extracts inhibit the synthesis of ergosterol, microtubules and DNA replication.
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6.6.20 ANTIGLYCEMIC AND ANTILIPIDEMIC EFFECTS It was reported that macroalgal cell wall polysaccharides had an ability to decrease TG (triglycerides) and cholesterol [27], but unfortunately this area of research for microalgae is not appropriately investigated. In spite Ginzberg and colleagues [452] reported that modified fatty acid profile improved carotene contents in chicken egg yolks after the injection of Porphyridium sulfated biopolymer. Furthermore, considerably low levels of insulin and glucose, VLDL, and serum cholesterol, and improved levels of hepatic cholesterol without any toxic effect were observed when polysaccharides of both Porphyridium and R. reticulate were used in combination in rats [453,454]. Huang et al. [242] suggested that sulfated polysaccharides of Porphyridium as potent antilipidemic (Fig. 6.12) and antiglycemic agent have the ability to reduce blood-glucose levels without any modification of islets of Langerhans. Due to rich contents of fibers, algal polysaccharides acts as bile acids binder, cation exchangers, and hypocholesterolemic agent could be used as nutraceuticals [455]. Algal-sulfated polysaccharides affect the absorption of nutrients, lower the lipid absorption and micelles formation, and make internal contents more viscous, and are therefore known as potent fibers [456]. They are equally effective in coronary heart disease by increasing bile excretion [457]. Fucans isolated from Sargassum polycystum were reported to have a significant antilipidemic effect in
FIGURE 6.12 Antilipidemic Mode of Action of Algal Sulfated Polysaccharides. : Inhibition by algal extract. Algal extract inhibits the synthesis of cholesterol via HMG 3hydroxy-3-methylglutaryl-CoA (HMG), isopentenylpyrophosphate squalene synthesis.
6.6 Therapeutic Applications of Algae
liver tissues and serum in hepatitis caused by acetaminophen toxicity [458]. Sulfated Sargassum wightii polysaccharide caused the normalization of lecithinecholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL) of plasma in nephrotoxicity [459]. Sulfated polysaccharides acted as potent renoprotective agent by reducing the LDL oxidation. Fucoidan from L. japonica were suggested as antilipidemic, showed their potency by raising LPL, HL (hepatic lipase), and LCAT, thus rendering LDL and TG levels while elevating HDL levels. Sulfated polysaccharides from F. vesiculosus affected the serum cholesterol and TG levels in dose-subsidiary-tone, e.g., smaller fractions of Ulva pertusa did not reduce the serum cholesterol, but only caused the normalization of TG by raising HDL [460]. It was observed that many sulfated biopolymers, by attracting the enzymes present on heparin-binding sites, influenced HL and LPL, e.g., fucoidan isolated from F. vesiculosus stabilized LPL activity by binding with heparin-binding sites [27]. Drug-toxicities-associated hyperlipidemia is effectively addressed by algal cell wall polysaccharides. Fucoidan polysaccharide sulfuric acid ester from L. japonica reduced the concentration of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL) of hyperlipidemic rats, and increased the concentration of high-density lipoprotein cholesterol (HDL). The treatment also increases the activities of lipoprotein lipase (LPL), hepatic lipoprotein (HL), and LCAT in serum [461]. Antilipidemic effect is also reported from the ulvan polysaccharide of U. pertusa [462].
6.6.21 ANTIALLERGY ACTIVITY Allergic diseases are one of the major public health problems in the developed world. It was estimated that approximately one-third of the general population was affected by allergic diseases. These diseases include asthma, dermatitis, beesting allergy, food allergy, conjunctivitis, and severe systemic anaphylaxis [463]. A large number of antiallergic agents from marine algae were identified. Several bioactive phloroglucinol derivatives, fucodiphloroethol G, eckol, dieckol, 6,6bieckol, phlorofucofuroeckol-A, and 1-(30 ,50 -dihydroxyphenoxy)-7-(200 ,400 ,6trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin isolated from E. cava are evidenced to be efficient against A23187 or Fc RI-mediated histamine release from KU812 and RBL-2H3 cells [464,465]. The red algae Carpopeltis affinis was confirmed to be effective against atopic allergic reactions in vitro [466]. The ethanolic extracts of edible red alga Laurencia undulata and brown alga E. cava exhibit a significant inhibition of all asthmatic reactions in OVA-induced mice [467,468]. Alginic acid, a naturally occurring hydrophilic colloidal polysaccharide obtained from several species of brown seaweeds, exhibits inhibitory effects against hyaluronidase activity and histamine release from mast cells [469]. Phycocyanin, one of the major pigment constituents of blue-green microalgae Spirulina, has been found to be an inhibitor of different allergic responses such as histamine release from rat peritoneal mast cells (Fig. 6.13), ear swelling in mice induced by OVA, and skin reactions in rats caused by histamine [470].
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FIGURE 6.13 Antiallergy Mode of Action of Algal Extract. : Inhibition by algal extract. Algal extract protects from allergic reactions by inhibiting the synthesis of prostaglandin E2.
6.6.22 ANTIFEEDENT ACTIVITY Antifeedent activity of two diterpenoids with a novel skeleton, dictyterepenoids A and B isolated from the brown algae Dilophus okamurae was reported against young abalone [471]. Crude organic extract of brown alga Dictyota pfaffii significantly exhibits antifeedent activity against sea urchin Lytechinus variegatus and generalist herbivore fishes [472].
6.6.23 ANTIADHESIVE EFFECT Algal cell wall polysaccharides are potent antiadhesive agents as they inhibited the pathogenic adhesion. Currently, several algal polysaccharides were isolated which affect the adherence of fish pathogens to skin, gills, and gut, and Helicobacter pylori to HeLa S3 [473]. Consequential impersonation of carbohydrate moieties of sulfated polysaccharides in provision of recognition sites for infection attachment was already been reported, e.g., heparin sulfates [474]. Antiadhesive property of heparin sulfate is contributed due to its molecular stereochemistry and net charge [475]. However, due to certain risk associated with use of sulfated polysaccharides as antiadhesive agent, further studies to understand cytotoxicity are needed.
6.6.24 BIOLUBRICATING AGENT Very little is known about the use of sulfated polysaccharides as biolubricants. However, Arad et al. [476] first time reported the lubricating properties of Porphyridium exopolysaccharides ascribable to its rheological idiosyncrasy [477]. Arad and coworkers suggested sulfated polysaccharides as better lubricating agent for joints than ordinary lubricating agents, i.e., hyaluronic acid, hydrogel, as they were thermostable [477]. In
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addition to these, they also reported that incubation of sulfated polysaccharide of Porphyridium with hyaluronidase did not show any significant change in viscosity while only 1% polysaccharide exhibited significant lubricating properties under high load. They concluded from their experiments that hyaluronic acid could be locum with sulfated biopolymers and could be used in the manufacturing of joint-lubricating solutions to alleviate the severity of arthritis.
6.6.25 DRAG-REDUCING AGENTS Very little is known for algal-sulfated polysaccharides as drag-reducing agents. Exclusively a couple of studies were made to check the drag-reducing potential of sulfated polysaccharides to extend their functional characteristics for engineering purposes. Gasljevic et al. reported that exopolysaccharides of microalgae have potential to act as drag reducers. Exopolysaccharides of both R. maculate and P. cruentum were found to be very potent drag reducers in very low concentration followed by Schizochlamydella [478].
6.6.26 OTHER APPLICATIONS It was reported that both micro- and macroalgae had their potential in nutraceuticals, functional foods, and health food industry [457]. Yet, due to their rheological characteristics and chemical composition, they also have diverse applications in other fields, e.g., cosmetics, prophylactic therapy. In conclusion to all applications of algal cell wall polysaccharides, adhesion is seemed to be more important as it is not only involved in algal movement but also in sand and soil particle aggregation, affecting cohesiveness and stability of sediments [479].
6.7 CONCLUSION This chapter briefly described algal classification and their possible pharmacological and therapeutic applications with respect to phytochemical constituents. This is an attempt to compile and document comprehensive information on different aspects of algae to help scientific community for further research and investigative study.
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6
Muhammad Ibrahim, Mahwish Salman, Shagufta Kamal, Saima Rehman, Aneeza Razzaq, Sajid Hamid Akash Government College University Faisalabad, Faisalabad, Pakistan
6.1 INTRODUCTION Algae are the group of plants known since ancient civilizations. Linnaeus introduced the term algae for the first time in 1753, and in 1789 de Jussieu classified the plants and separated algae from the rest of the plants. This classification is accepted till date [1]. The word “algae” is derived from the Latin word “alga” which means seaweeds [2]. The study of algae is called phycology (phyco means algae and logos means study of). Phycos is a Greek word which means seaweeds. The history of algae is mentioned in the early Chinese, Roman, and Greek literatures. Roman named it Fucus, whereas Chinese called it Tsao. The ancient Hawaiians used algae as food and called them Limu. The algae were used as manure on the north coast of France as early as 12th century [3,4]. They are eukaryotic and predominantly aquatic, photosynthetic organisms, which range in size from tiny flagellate micromonas that is 1 mm (0.000039 in.) in diameter to giant kelps that reach 60 m (200 ft) in length [5]. Biologists divided the living organisms into five kingdoms named as animals, plants, fungus, protists, and prokaryotes [6]. Algae belong to protista kingdom. Protists often share certain morphological and physical characteristics with animals, plants, and fungi. However, protists are neither animals nor plants, and nor fungi [5]. In earlier classifications, algae, which are photosynthetic like plants, were placed in the kingdom planta. Most of the classifications have now removed algae from the plant kingdom due to their simple construction (majority being unicellular), variety of accessory pigments used for photosynthesis, lack of protecting tissue around gametic cells, and their highly varied life histories [7]. Although, algae are photosynthetic organisms, they lack specialized reproductive systems of the plants, which always have multicellular reproductive structures that contain fertile gametes surrounded by sterile cells. Algae also lack true stems, leaves, and roots [5]. Algae are photosynthetic organisms, which contain chlorophyll and other photosynthetic pigments. These pigments trap light energy coming from the sun, convert it into chemical energy, and store it in the form of photosynthetic products such as starch, carbohydrates, and various complex sugars [8]. Their photosynthetic efficiency is higher than other plants, and some species of algae are considered among Algae Based Polymers, Blends, and Composites. http://dx.doi.org/10.1016/B978-0-12-812360-7.00006-9 Copyright © 2017 Elsevier Inc. All rights reserved.
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the fastest growing organisms. It is estimated that photosynthetic efficiency of algae ranges from 3% to 8%, compared to 0.5% of many other terrestrial crops [9]. As the algae cells are complete simple organisms capable of photosynthesis and synthesis of a multitude of other compounds that make up the cell, they have attracted special interest from the biological and phytochemical scientists [10]. The purpose of this chapter is to give brief information about algae and their biologically active constituents. The isolation and characterization of the biologically active components from seaweeds have gained much attention from various research groups across the world and the seaweeds have become a recognized potential natural product in pharmaceutical industries.
6.2 OCCURRENCE Algae have universal occurrence and are found in almost all types of habitats. They are found in freshwater, seawater, on rocks, soil, stones, on other plants and even on animals, in deserts, and on permanent snowfields etc. [11,12]. They sometimes appear in such large quantity that the landscape becomes colored due to the presence of pigments in their cells. The once-mysterious “red snow” is now known to be due to the presence of algae rich in red pigments that mask the green chlorophyll. On the other hand, some algal species grow in hot springs even at a high temperature of 900001 C [13].
6.3 GENERAL CHARACTERS OF ALGAE Algae are chlorophyllous autotrophic organisms [14]. Most of the algae are aquatic; some are terrestrial [14]. They possess thalloid plant body without any variation of plant tissues [14]. They lack vascular tissues (xylem and phloem) and epidermis with stomata [14]. The sex organs are mostly unicellular [14]. Both gametophytic and sporophytic generations are independent in the life cycle of algae [14]. There is no formation of embryo after gametic union [14]. The germination of zygote can be of direct or indirect type [2]. All kinds of reproductions, sexual, asexual, and vegetative, are found in algae [2].
6.4 CLASSIFICATION OF ALGAE Classification is a scientific categorization of organisms in hierarchical series of groups [11]. Harvey is considered as one of the first algologist who gave the first descriptive algal classification [1]. Although different scientists classified algae in a number of ways, according to the structure of algae, it can be classified into two main groups, i.e., microalgae and macroalgae. Microalgae are unicellular organisms, and that means they have only one cell with complex and robust cell walls, whereas macroalgae are multicellular, have complex structures, and look like plants. Based
6.4 Classification of Algae
on the coloring pigments present in macroalgae, they are further divided into three large groups, i.e., red, green, and brown algae [9]. In the older classifications, algae actually were simply divided into four groups, i.e., Phaeophyceae or brown algae, Chlorophyceae or green algae, Rhodophyceae or red algae, and Cyanophyceae or blue-green algae. However, now there is more knowledge about simpler organisms, which were not used to be considered as algae, it has been realized that there is no real reason for such a distinction, and therefore the number of groups is increased. At present, it is most convenient to divide algae into 10e11 classes [15,16]. Generally, algae are categorized into different classes on the basis of nature and properties of pigments, nature of reserve and storage products, type, number, insertion and morphology of flagella, chemical composition and physical features of cell wall, and morphology and characteristics of cells and thalli [10,17].
6.4.1 CHLOROPHYCEAE (GREEN ALGAE) Chlorophyceae or green algae are a large and diverse group of organisms consisting more than 700 species [17]. Green algae occur in wide range of habitants. They are found in aquatic, amphibious, terrestrial, as well as subaerial conditions. They are principally freshwater species but are also found in seawater. Green algae are eukaryotes characterized by chlorophyll a and b as major photosynthetic pigments. Majority of the unicellular green algae contain one chloroplast per cell. They store their food as true starch and have quite rigid cell walls composed of cellulose with pectic substances incorporated into the wall structure. Motile gametes possess two, or multiples of two, equal and terminated inserted flagella [11,13,14,17].
6.4.2 XANTHOPHYCEAE (YELLOW-GREEN ALGAE) Xanthophyceae (yellow-green algae) are represented by 16 genera and 376 species [18]. Most of the members of xanthophyceae are found in free-floating freshwater conditions. Some are found attached to the walls or tree trunks, while others are soil inhabitants. A few representatives are also marine [11,18]. These yellowgreen algae were once classified with the green algae. However, their pale green or yellow-green coloration indicates that they have a unique group of pigments. The main pigment in these algae is xanthophyll along with chlorophyll a and e. Pyrenoids are absent. Reserve food material is oil (glucan and lipids). Their cell walls are composed of cellulose and pectin. Motile gametes possess two or more anterior and unequal flagella, of which larger one is pantonematic-type and smaller is acronematic. In structure xanthophyceae shows similarity with Chlorophyceae [10,11,14,18].
6.4.3 CHRYSOPHYCEAE (GOLDEN ALGAE) Members of this class contain phycochrysin pigment which imparts brown or orange color to the algae. Motile cells possess one or two equal or unequal and dissimilar
157
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flagella. One of the flagellum is anteriorly directed, long, hairy, and pantonematictype, while the second one is posteriorly directed, short, smooth, and acronematictype. Reserve food material is oil and chrysolaminarin. Cellulose is absent in the cell wall which has a tendency to become silicified [14].
6.4.4 BACILLARIOPHYCEAE (YELLOW OR GOLDEN-BROWN ALGAE) Bacillariophyceae or golden-brown algae are unicellular microorganisms, popularly called as diatoms, containing about 190 genera and are classified into 5500 species [18]. It is the largest unicellular class of algae and most widely spread of all the unicellular algae. It occurs in all types of habitats except in hot waters and extremely dry areas. They are found in both freshwater and salt water and in the moist soil. Abundant in cold waters. The yellow or golden-brown color is due to higher proportion of carotenoids and xanthophylls, diatoxanthin, diadino, and fucoxanthin. Their reserve food material is fat; motile structures are almost absent; and pyrenoids are present. Their cell wall is composed of silica and partially of pectin substances [2,14,18].
6.4.5 CRYPTOPHYCEAE The color of this class varies from brown, red, or olive green to even blue-green due to the presence of different types of pigments. Photosynthetic pigments include biloproteinsddifferent from those of red algae and blue-green algae. They are unicellular, motile, and naked. Flagella are usually equal and located at the anterior end of the cell. Both are band-shaped [14].
6.4.6 DINOPHYCEAE Members of this class, commonly known as dinoflagellates, are dark yellow or brown with characteristic combination of pigments, chlorophyll a and c, and carotenoids (dinoxanthin and peridinin). Members are unicellular and biflagellate. One of the flagellum is acronematic-type whereas the second is in helical form, and described as band shaped. Cells contain many discoid chloroplasts with pyrenoids [14].
6.4.7 CHLOROMONADINEAE Members of this class are bright green in color, unicellular, and biflagellate. Chromatophores are numourous, discoid, and without pyrenoids. Sexual reproduction is absent. Reserve food is fat and oil. The flagella originate from the anterior depression. Of the two, one is anteriorly directed and bears hair, and the second is posteriorly directed and smooth [14].
6.4.8 EUGLENINEAE Members of this class almost resemble to those of Chlorophyceae in having green color, which is due to excess of chlorophyll. The chloroplasts can be discoid or
6.4 Classification of Algae
stellate. Their reserve food material is paramylum, with a number of pantonematictype of flagella, may be 1, 2, or 3. They reproduce by cell division [14].
6.4.9 PHAEOPHYCEAE (BROWN ALGAE) Phaeophyceae or brown algae are represented by about 240 genera and over 1500 species of which 99.7% are marine [11] and live attached to the rocks around sea coasts. They therefore occupy same kinds of habitat as the red algae. Brown algae grow as attached not only to the rocks but also to the dykes, quays-attached mollusks, eelgrass, or even other seaweeds [11,19]. These are multicellular algae and comprise a brown pigment which is responsible for their characteristic brown color and the common name of brown algae or brown seaweeds. They are structurally quite complex [10]. The brown algae owe their color to the pigment fucoxanthin. Fucoxanthin is present in large quantity and masks the green color of the chlorophylls. Other pigments include chlorophyll a, c, b-carotene, violaxanthin, flavoxanthin, etc. Their photosynthetic products are polysaccharides, fats, traces of simple sugars, and alcohols. Food is stored in the form of soluble carbohydrate called laminarin and an alcohol called mannitol. The cell wall is composed of cellulose, fuicinic acid, and alginic acid. The flagellated motile cells are pyriform and bear two laterally borne flagella, of which one is longer, anteriorly directed and pantonematic type and the second one is short, posteriorly directed and acronematic-type [14].
6.4.10 MYXOPHYCEAE (CYANOPHYCEAE) The class Myxophyceae or Cyanophyceae is commonly called as blue-green algae because of the presence of a principal bluish-green pigment (c-phycocyanin) along with chlorophyll a, b-carotene, and some quantity of Myxoxanthin, Myxoxanthophyll as well as small quantities of carotene, flavacin, and c-phycoerythrin [11]. They can be unicellular or multicellular, free-living or colonial, unbranched filamentous or branched filamentous, and acquatic or terrestrial in nature [1]. The bluegreen algae are also known as Cyanobacteria because they resemble to bacteria [19]. The photosynthetic reserve food of blue-green algae is glycogen. Motile flagellated cells are altogether absent, cellular organization is simple prokaryotic type lacking membrane-bound cell organelles such as nucleus, chromatophores, dictyosomes, ER, and true vacuoles. Cells lack definite chromosomes and divide by simple fission [14].
6.4.11 RHODOPHYCEAE (RED ALGAE) The red algae are a distinct lineage of eukaryotic algae, containing about 5000e6000 species [20]. The majority of red algae live in tropical marine habitats, and most of the species are multicellular. Red algae have a complex life history, which means they go through several stages of independent organisms to complete their life cycles. Most undergo sexual reproduction. Like many other
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algae, rhodophytes also contain a phosynthetic pigment chlorophyll and are able to photosynthesize their own food. These algae contain reddish pigment phycoerythrin in a large amount; the red color of these algae is due to the presence of this pigment [21]. Other pigments include chlorophyll a and d, carotenoids (a- and b-carotenes), and xanthophylls (taraxanthin, lutein, zeaxanthin, etc.). Reserve food is stored in the form of floridean starch and galacto-fructosides. Their cell wall is mainly composed of cellulose and pectin, and in addition some components of polysulfate esters of carbohydrates also occur. Majority of the red algae exhibit triphasic life cycles but some also exhibit biphasic life cycles [14].
6.5 BIOLOGICALLY ACTIVE COMPOUNDS EXTRACTED FROM ALGAE 6.5.1 SULFATED POLYSACCHARIDES Sulfated polysaccharides are the polysaccharides present in the cell wall of algae, which play storage and structural roles in seaweeds, and may exhibit many interesting biological properties. Seaweeds are the main source of sulfated polysaccharides [22,23]. The details of these compounds are briefly summarized in Table 6.1.
6.5.2 POLYPHENOLIC COMPOUNDS Phenolic compounds comprise a wide variety of molecules that have a polyphenol structure. Polyphenols are divided into several classes according to the number of phenol rings they contain and the structural elements that bind these rings to one another. The main groups of polyphenols are flavonoids, phenolic acids, tannins (hydrolyzable, condensed, and phlorotannin), stilbenes, and lignans [32].
6.5.3 FLAVONOIDS Flavonoids are the natural products that consist of C6eC3eC6 carbon framework, or more specifically phenylbenzopyran functionality. Depending on the position of the linkage of aromatic ring to the benzopyran moiety, flavonoids can be divided into three classes [33]. • • •
Flavonoids (2-phenylbenzopyrans) Isoflavonoids (3-benzopyrans) Neoflavonoids (4-benzopyrans) The details of these compounds are briefly summarized in Table 6.2.
6.5.4 PHLOROTANNINS Phlorotannins are phenolic compounds formed by polymerization of phloroglucinol (1,3,5-trihydroxybenzene) monomer units and biosynthesized through the
Table 6.1 Sulfated Polysaccharides: Biologically Active Compounds Extracted From Algae Sr. No.
Name
Molecular Formula
Biological Source
Biological Use
1
Heparin
C12H19NO20S3
Red alga Delesseria sanguinea
Anticoagulant, antiinflammatory, and antimetastastic effects
2
Agar
3
Chrysolaminarin
4
Lambda (l)carrageenan
C14H26O19S3
5
Iota (i)carrageenan
C14H24O15S2
Constit. of red seaweed Eucheuma spinosum
Antioxidant
[27]
6
Kappa (k)carrageenan
C14H25O12S
Constit. of red seaweed Kappaphycus alvarezii
Antioxidant
[27]
7
Fucans
Isol. from Analipus japonicas, Ascophyllum nodosum, Chorda filum, Fucus evanescens, and Laminaria saccharina
Anticoagulant
References [24]
[25]
Reserve carbohydrate Antiviral, antioxidant
N/A
[26] [27]
N/A
[27]
Continued
6.5 Biologically Active Compounds Extracted From Algae
Extracted from red marine algae (Rhodophyceae); Gelidiella acerosa, Gelidiella various Gelidium spp. Gracilaria confervoides, Pterocladia capillacea, and Pterocladia lucida Isol. from diatoms and related algae Isol. from species of the Gigartina and Chondrus genera
Structure
161
162
Sr. No.
Name
Molecular Formula
Biological Source
8
Alginate
(C6H8O6)n
Constit. of red and brown algae
9
Ulvan
10
Sulfated mannans
11
Rhamnan sulfate
12
Laminarin
Isol. from cell walls of marine green algae Ulva rigida, Ulva pertusa, and Ulva lactuca Present in red and green seaweeds
Present in cell walls of Monostroma latissimum and Monostroma nitidum
(C6H10O5)n
Constit., constituents; Isol., isolated.
Found in brown algae especially the Laminaria subgroup; isol. from Laminaria cloustoni
Biological Use
Structure
References [28]
Shows cytotoxic props. Antioxidant
N/A
[29]
Inhibit the propagation of HSV-1 in Vero cells Antiviral
N/A
[30]
Anticoagulant; antilipemic agent; plant activator
[31]
[26]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.1 Sulfated Polysaccharides: Biologically Active Compounds Extracted From Algaedcont’d
Table 6.2 Flavonoids: Biologically Active Constituents Extracted From Algae Name
1
40 -Chloro-2-
Molecular Formula C15H11O3Cl
hydroxyaurone
Biological Source Constit. of brown algae Spatoglossum variabile
Biological Use
Structure O
Antioxidant
References [34]
H H
O Cl
2
40 -Chloroaurone
C15H9O2Cl
Constit. of brown algae S. variabile
O
Antioxidant
[34]
O
Cl
3
Morin
C15H10O7
Constit. of green algae Caulerpa serrulata
HO
Antioxidant HO
OH O
4
Hesperidin
C28H34O15
Constit. of red algae
Antioxidant
5
Myricetin
C15H10O8
Constit. of Tubinaria ornate, Chondrus verruscosus
Antioxidant
OH
[35]
O OH
[35]
OH OH HO
O
OH
O
[35]
OH OH
Continued
6.5 Biologically Active Compounds Extracted From Algae
Sr. No.
163
164
Sr. No.
Name
Molecular Formula
6
Quercetin
C15H10O7
Biological Source
Biological Use
Constit. of Undaria pinnatifida and Padina arborescens
Antioxidant
Structure OH HO
(0003)-Catechin (2S,3R)
C15H14O6
Constit. of red alga Acanthophora spicijka
OH
[35]
O
OH
7
References
O
OH
OH
Antioxidant HO
OH
[36]
O OH OH
8
Apigenin
C15H10O5
Constit. of Acanthophora spicifera
Analgesic and antiinflammatory
HO
OH
[37]
CH3
[38]
O
OH O
9
Scutellarein 40 methyl ether
C16H12O6
Constit. of Osmundea pinnatifida
Antileishmanial
O HO HO
Constit., constituents.
O
OH O
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.2 Flavonoids: Biologically Active Constituents Extracted From Algaedcont’d
6.5 Biologically Active Compounds Extracted From Algae
acetateemalonate pathway, also known as polyketide pathway. Phlorotannins are highly hydrophilic components with a wide range of molecular sizes ranging between 126 Da and 650 kDa. Based on the types of linkage, phlorotannins can be classified into four subclasses such as [39]: • • • •
Fuhalols and phlorethols (phlorotannins with an ether linkage) Fucols (with a phenyl linkage) Fucophloroethols (with an ether and phenyl linkage) Eckols (with a dibenzodioxin linkage) The details of these compounds are briefly summarized in Table 6.3.
6.5.5 TERPENES AND TERPENOIDS Terpenes are the hydrocarbons composed of carbon and hydrogen, and are the compounds whose carbon skeleton can be divided into two or more units identical with the carbon skeleton of isoprene. They are formed by bonding the tail of one isoprene unit to the head of another. Terpenes can be oxygenated into terpeneealcohols, terpeneeesters, terpeneeoxides, terpeneeketones, terpeneealdehydes, terpenee esters, and other varieties of oxygenated compounds [71,72]. The details of these compounds are briefly summarized in Table 6.4.
6.5.6 PHYCOBILIPROTEINS Phycobiliproteins (PBPs) are the important photosynthetic accessory pigment biomolecules assembled into a supramolecular light-harvesting antenna complex, phycobilisomes (PBS), in cyanobacteria and red algae [145]. The details of these compounds are briefly summarized in Table 6.5.
6.5.7 STEROLS Sterols are steroids carrying a hydroxyl group at C-3 [146]. Sterols are a type of lipids found in both plants and animals. Although sterols are classified as lipids, they differ significantly from triglycerides and phospholipids in structure and function. Sterol molecules consist of multiple rings made primarily of carbon and hydrogen atoms that are attached to each other [147]. The details of these compounds are briefly summarized in Table 6.6.
6.5.8 POLYHYDROXYALKONATES Polyhydroxyalkonates (PHAs) are polyesters of various hydroxyalkanoates that are synthesized by many gram-positive and gram-negative bacteria in at least 75 different genera. These polymers are accumulated intracellularly to levels as high as 90% of the cell dry weight under conditions of nutrient stress and act as a carbon and energy reserve. The molecular mass of PHAs varies per PHA producer, but is
165
166
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algae
1
2
3
Name 1,2,3,5-Benzenetetrol; 2,5-O-disulfate
1,2,3,5Benzenetetrol,2-Osulfate
1,3,5-Benzenetriol
Molecular Formula C6H6O10S2
C6H6O7S
C6H6O3
4
Benzo[1,2-b:3,4-b0 ]bis [1,4]benzodioxin1,3,6,9,11-pentol
C18H10O9
5
4000 ,7-Bieckol
C36H22O18
Biological Source
Biological Use
Constit. of brown algae Ascophyllum nodosum, Petalonia fascia, Scytosiphon lomentaria, Chorda filum, Fucus distichus spp. anceps, Fucus vesiculosus, Pelvetia canaliculata, and Dictyota dichotoma Constit. of brown algae P. fascia, S. lomentaria, D. dichotoma, A. nodosum, F. vesiculosus, and Himanthalia elongata
Biogenetic precursor of the wide range of oligomeric phlorotannins which are a major component of brown algae
A minor constit. of brown algae, e.g., Halidrys siliquosa, Cystophora retroflexa, Eisenia arborea, Laminaria ochroleuca, Analipus japonicus, Cystophora congesta, and Carpophyllum angustifolium Constit. of brown algae E. arborea, Ecklonia maxima, and Ecklonia stolonifera
Spasmolytic agent, hyaluronidase inhibitor
Constit. of brown algae E. maxima, E. arborea, and Eisenia bicyclis
Structure
References
OH O
O O
HO
OH
O
S O
[40]
S
OH
O
OH
[41,42] O
O S O
OH
OH
HO
OH
HO
[43]
OH
[44]
[45]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
6,60 -Bieckol
C36H22O18
Constit. of brown algae Ecklonia kurome and E. arborea
Antiplasmin inhibitor; a2-macroglobulin inhibitor; exhibits antiHIV activity, antioxidant
[44]
7
8,80 -Bieckol
C36H22O18
Constit. of brown algae E. kurome and E. arborea
Antiplasmin inhibitor; a2-macroglobulin inhibitor, hyaluronidase inhibitor
[44]
8
2,20 ,4,40 ,6,60 Biphenylhexol
C12H10O6
Occurs in several brown algae, e.g., F. vesiculosus, C. retroflexa, C. angustifolium
HO
OH
6.5 Biologically Active Compounds Extracted From Algae
6
[46]
HO
OH HO
9
2-Chloro-1,3,5benzenetriol
C6H5ClO3
Constit. of Rhabdonia verticillata and from brown algae E. arborea and C. angustifolium
OH
Cl HO
[47] OH
167
OH
Continued
Name
Molecular Formula
10
Decafuhalol-A
C60H42O35
Constit. of brown algae Sargassum spinuligerum and C. angustifolium
11
Dieckol
C36H22O18
Constit. of brown algae E. kurome and Ei. bicyclis
12
Difucophlorethol-A
C24H18O12
Isol. from brown algae H. elongata, C. retroflexa, Cystophora torulosa, and Xiphophora chondrophylla
[51,52]
13
Dihydroxyfucotriphlorethol-B
C30H22O17
Isol. from brown algae S. spinuligerum and C. angustifolium
[53]
Biological Source
Biological Use
Structure
References [48]
Inhibitor of a2macroglobulin, glycation and a-amylase
[49,50]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
168
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d
C18H12O9
Constit. of brown algae E. kurome, E. maxima, E. arborea, and Ei. bicyclis
[49]
15
Fucodifucotetraphlorethol-A
C48H34O24
Isol. from brown algae C. torulosa, S. spinuligerum, and C. angustifolium
[53]
16
Fucodiphlorethol-D
C24H18O12
Isol. from brown algae Cystoseira baccata, C. congesta, C. angustifolium, S. spinuligerum, and C. retroflexa
[54]
17
Fucodiphlorethol-D; 4000 -hydroxy
C24H18O13
Isol. from brown algae S. spinuligerum, Carpophyllum maschalocarpum, and C. torulosa
[55,56]
18
Fucodiphlorethol-E
C24H18O12
Isol. from brown algae Durvillaea antarctica, S. spinuligerum, C. torulosa, and F. vesiculosus
[55]
169
Eckol
6.5 Biologically Active Compounds Extracted From Algae
Inhibitor of a2macroglobulin, glycation, and a-amylase
14
Continued
170
Sr. No.
Name
Molecular Formula
Biological Source
Biological Use
19
Fucophlorethol-A
C18H14O9
Constit. of F. vesiculosus
Hyaluronidase inhibitior
20
2,30 ,4,40 ,50 ,6Hexahydroxydiphenyl ether
C12H10O7
Constit. of Bifurcaria bifurcata, Halidrys sp., C. angustifolium, and other brown algae
21
1-C-Methyl-scylloinositol
C7H14O6
Isol. from red alga Polysiphonia fastigiata and brown algae
Structure
References [57]
[58]
OH
[59] OH
HO
OH HO HO
22
4-C-Methyl-myoinositol; D-form
C7H14O6
Isol. from red algae, e.g., P. fastigiata and brown alga, e.g., Laminaria cloustoni
Osmoregulator, especially in brown algae frequently exposed to both fresh water and salt water
OH
[59]
HO
HO
OH
OH
OH
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d
C54H38O31
Constit. of brown algae Sargassum muticum, S. spinuligerum, C. maschalocarpum, and C. angustifolium
[60]
24
Octafuhalol-A
C48H34O28
Constit. of brown algae S. muticum, S. spinuligerum, C. maschalocarpum, and C. angustifolium
[61]
25
Pentafucol-A
C30H22O15
Isol. from brown algae Scytothamnus australis and A. japonicas
[62,63]
26
2,30 ,4,50 ,6Pentahydroxydiphenyl ether
C12H10O6
[64]
27
Pseudoheptafuhalol-B
C42H30O24
Constit. of brown algae including A. japonicus, L. ochroleuca, Sargassum thunbergii, Ecklonia bicyclis, H. elongata, B. bifurcata, Cystoseira tamariscifolia, C. congesta, and S. muticum Constit. of brown algae S. spinuligerum and C. angustifolium
171
Nonafuhalol-A
6.5 Biologically Active Compounds Extracted From Algae
23
[65]
Continued
172
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d Name
Molecular Formula
28
Pseudoheptafuhalol-C
C42H30O24
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
29
Pseudoheptafuhalol-D
C42H30O24
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
30
Pseudohexafuhalol-B
C36H26O21
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
Biological Source
Biological Use
Structure
References
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
Pseudohexafuhalol-C
C36H26O2
Constit. of brown algae S. spinuligerum and C. angustifolium
[65]
32
Pseudotetrafuhalol-A
C24H18O14
Constit. of algae C. maschalocarpum and S. spinuligerum
[65]
33
Terfucohexaphlorethol-A
C60H42O30
Isol. from brown algae C. retroflexa, C. maschalocarpum, and C. angustifolium
[52,56]
34
Terfucopentaphlorethol-A
C54H38O27
Isol. from brown algae C. retroflexa and Carpophyllum maschalocarpum
[56]
6.5 Biologically Active Compounds Extracted From Algae
31
173
Continued
174
Sr. No.
Name
Molecular Formula
35
[1,10 :30 ,100 -Terphenyl]-
C18H14O9
Constit. of various brown algae incl. A. japonicus, B. bifurcata, F. vesiculosus, and H. elongate
[45,66]
36
Tetrafucol-A
C24H18O12
Constit. of brown algae F. vesiculosus, A. japonicas, and C. angustifolium
[62]
37
Tetraphlorethol-C
C24H18O12
Constit. of algae L. ochroleuca, C. congesta, E. maxima, Cystophora reflexa, S. spinuligerum, and C. angustifolium
[54]
38
1-(2,4,6Trihydroxyphenyl)5,8,11,14,17eicosapentaen-1-one; (all-Z)-form
C26H34O4
[67]
39
1-(2,4,6Trihydroxyphenyl)-
C24H32O4
Constit. of brown algae Zonaria turneriana, Zonaria diesingiana, Zonaria farlowii, Zonaria tournefortii, and Distromium decumbens Isol. from brown algae Cystophora spp.
2,20 ,200 ,4,40 ,400 ,6,60 ,600 nonol
Biological Source
Biological Use
Structure
References
[68]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.3 Phlorotannins: Biologically Active Compounds Extracted From Algaedcont’d
6,9,12,15octadecatetraen-1one; (all-Z)-form Triphlorethol-A
C18H14O9
Constit. of C. congesta and other brown algae
41
Triphlorethol-B
C18H14O9
Constit. of brown algae E. kurome, E. stolonifera, C. baccata, and C. angustifolium
42
Undecafuhalol-A
C66H46O38
Constit. of brown algae B. bifurcata, Landsburgia quercifolia, C. angustifolium, and S. spinuligerum
Constit., constituents; Isol., isolated.
[69]
Shows antitrypsin and antiplasmin activities
[47]
[70]
6.5 Biologically Active Compounds Extracted From Algae
40
175
176
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algae
1
Name 2-[2-(Acetyloxy)ethenyl]-6,10dimethyl-2,5,9-undecatrienal
Molecular Formula C17H24O3
Biological Source
Biological Use
Penicillus capitatus and Udotea cyathiformis
Antibacterial and ichthyotoxin
Structure
References [73]
O O
2
Adonixanthin
C40H54O3
O OH
Isol. from green algae
[74]
HO O
3
1(10)-Aristolen-9-ol; (ent-9a)-form
C15H24O
Constit. of marine algae
4
9-Aristolen-1-ol; (ent-1b)-form
C15H24O
Constit. of Nardostachys chinensis, Nardostachys grandiflora, and marine algae
5
1,2-Benzenedicarboxylic acid; dibutyl ester
C16H22O4
Reported from Penicillium bilaii. Streptomyces nasri, and Streptomyces melanosporofaciens. Also isol. from various red algae
OH
OH
Insect repellent; now superseded; glycosidase inhibitor
[75]
[76]
[77] O O O O
6
C34 Botryococcene; 1,2,6,7,21,22,24,29Octahydro
C34H66
Constit. of lacustrine sediments attributed to algae
[78]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
7
8
3-Bromo-4,5dihydroxybenzaldehyde
3-Bromo-4,5dihydroxybenzoic acid
C7H5BrO3
C7H5BrO4
Constit. of red algae Polysiphonia spp. and sponge Psammaplysilla purpurea Constit. of Indian algae
Br
Antibiotic
[79]
HO O HO O
OH
OH OH
9
10
3-Bromo-4hydroxybenzaldehyde
C7H5BrO2
3-Bromo-4-hydroxybenzoic acid
C7H5BrO3
Br
Isol. from Asparagopsis taxiformis, P. purpurea, and Rhodomela larix; constit. of Indian algae Constit. of Indian algae
[81]
HO O Br
[82]
HO
O
OH
11
6-(1,3-Butadienyl)-1,4cycloheptadiene; (R)-form
C11H14
Isol. from brown algae Desmarestia aculeata and Desmarestia viridis
Algal gamete sex attractant
[83]
12
3-(1-Butenyl)-4vinylcyclopentene; (3S,4S)-(Z)form, 30 ,40 -Didehydro
C11H14
Isol. from brown algae D. aculeata, D. viridis, and Syringoderma sp.
Algal gamete sex attractant
[84,85]
13
6-Butyl-1,4-cycloheptadiene; (R)-form
C11H18
Isol. from brown algae Dictyopteris spp. and Dictyota dichotoma
[86,87]
177
Continued
6.5 Biologically Active Compounds Extracted From Algae
Br
[80]
178
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
Biological Source
Biological Use Antibiotic, weakly active against gram-positive and gram-negative bacteria and blue-green algae; spore germination inhibitor
Structure
References
14
Colletodiol; 9,10-dihydro, 11,12-diketone
C14H18O6
Constit. of Colletotrichum capsici, Cytospora sp.
15
Crustaxanthin; tetraketone
C40H48O4
Found in fish, crustaceans, bacteria (Mycobacterium laticolum), and algae (Euglena)
[89]
16
b-Cryptoxanthin
C40H56O
Isol. from papaya (Carica papaya) and many other higher plants, also from fungi, diatoms blue-green algae and fish eggs Constit. of diatoms, algae, and fish
[90]
17
Diatoxanthin
C40H54O2
18
2,10-Dibromo-3-chloro-5,10epoxy-8-chamigren-7-ol
C15H21Br2ClO2
[88]
HO
HO
[91,92]
Cl
[93]
HO
19
2,3-Dibromo-4,5dihydroxybenzaldehyde
C7H4Br2O3
3,5-Dibromo-4-hydroxybenzyl alcohol
C7H6Br2O2
Constit. of red algae Laurencia pacifica, Laurencia majuscula, Laurencia nidifica, Laurencia claviformis, and Laurencia marianensis and the mollusk Aplysia dactilomela Isol. from algae Polysiphonia lanosa and R. larix
Feeding deterrent for aphids, insecticide, antimitotic agent
Br
O
Br OH
Br
O
HO
20
Isol. from red algae Polysiphonia spp. and R. larix and Rhodomela confervoides
[94,95] Br
HO
Br
[96]
HO OH Br
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
21
3,4-Dibromo-5-hydroxymethyl1,2-benzenediol
C7H6Br2O3
Isol. from red algae Lenormandia prolifera, Polysiphonia, Odonthalia, and Rhodomela spp.
Br
Glucosidase inhibitor
[79,97]
Br
OH
OH OH
22
24
25
2,4-Dibromophenol
2,6-Dibromophenol
2,6-Di-tert-butyl-4-ethylphenol
C7H10Br2O2
C6H4Br2O
C6H4Br2O
C16H26O
Isol. from red algae Bonnemaisonia hamifera and Bonnemaisonia nootkana Isol. from the acorn worms Balanoglossus carnosus and Ptychodera sp. Commonly found in marine algae, e.g., Grateloupia elliptica, mollusks, and crustaceans Widespread in marine algae, fish, mollusks and crustaceans, such as Barantolla lepte, Marphysa sanguinea, Glycera americana, Lumbrineris latreilli, Nephtys australiensis, Ceratonereis aequisetis, Australonuphis teres, Scoloplos normalis, Penaeus plebejus, Penaeus latisulcatus, Penaeus merguiensis, Platycephalus caeruleopunctatus, Nemadactylus douglasii, Polysiphonia sphaerocarpa, Ulva lactuca, Ptychoderma flava laysanica, and Capitella sp Metabolites of blue-green algae
HO
[98] O Br
Br
Br
Br
[99,100]
OH
Important flavor component of marine fish, mollusks and crustaceans
Br
[101,102]
OH Br
Antioxidant
[103]
6.5 Biologically Active Compounds Extracted From Algae
23
2-(Dibromomethylene) hexanoic acid
HO
179
Continued
180
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
26
2,3-Didehydro-3,30 -dihydroxy-
C40H52O3
b,ε-caroten-4-one
Biological Source
Biological Use
Structure
References
Constit. of Akategani estuarine crab Sesarma haematocheir, green algae, and goldfish
[104]
HO
O OH
27
5,6-Dihydro-3-[2-(4hydroxyphenyl)-2-oxoethyl]2(1H)-pyridinone,
C13H13NO3
Isol. from an algae-infested Caribbean sponge Halichondria melanodocia
OH
O
28
4,18-Dihydroxy-1(9),6,13xenicatrien-19-al
C20H32O3
[105]
O
N H
Brown algae D. dichotoma
[106] HO
HO O
29
3,5-Diiodothyronine; (S)-form
C15H13I2NO4
O
Occurs in proteins of marine algae
HO
[107] NH2
I O I
OH
30
Dilophol
C20H34O
Constit. of algae Dilophus ligulatus and D. dichotoma
[108]
OH
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
Echinenone
C40H54O
Found in echinoids, crustacean and green algae
32
Echinenone; 4-Alcohol
C40H56O
Isol. from blue-green algae
33
Echinenone; 3S-Hydroxy
C40H54O2
Isol. from Adonis annua, Rhizobium lupini, fish eggs, algae
34
Echinenone; 40 -Hydroxy
C40H54O2
O
[109]
HO
[110]
O
[111]
HO
Isol. from the spindle shell Fusinus perplexus, goldfish eggs, green algae, and other spp.
[111]
O
OH
35
Galactaric acid
C6H10O8
Isol. from brown algae, various fruits and fungi
Used as 2% aq. solution to form color complexes with Fe, Co, Cr(III), Mn, U(VI). (pH 3e10)
HO
[112]
OH OH
O HO
O
6.5 Biologically Active Compounds Extracted From Algae
31
HO
Continued
181
OH
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d
36
Name Grahamimycin-B
Molecular Formula C14H20O7
Biological Source Isol. from Cytospora sp.
Biological Use
References
O
[113]
OH O
HO O
O
O
37
1-Heptadecene-4,6,8,10,12pentol; (4S,6S,8R,10R,12R)form, Penta-Me ether
C22H44O5
Isol. from the blue-green algae Scytonema burmanicum and Scytonema mirabile
[114] O O O
O O
38
1-(1,3-Hexadienyl)-2vinylcyclopropane; (1R,10 E,2R,30 Z)-form
C11H16
Constit. of algae Dictyopteris spp.
39
Hyatellaquinone; (þ)-form
C22H30O4
Constit. of Hyatella intestinalis and Spongia sp.; isol. from red algae
[115]
HIV reverse transcriptase (HIV-rt) inhibitor
[116]
O O O OH
40
3-(2-Hydroxy-4,8-dimethyl3,7-nonadienyl)benzaldehyde; Ac
C20H26O3
O
Constit. of green algae Halimeda scabra, Halimeda macroloba, and Halimeda discoidea
[117]
O
O
41
10-Hydroxy-4-oplopanone; (þ)-form
C15H26O2
Constit. of soft coral Nephthea sp. and the algae Laurencia subopposita
42
18-Hydroxy-1(9),6,13xenicatrien-19-al; Ac
C22H34O3
Constit. of marine algae D. dichotoma and Pachydictyon coriaceum
O
[118]
HO
O O O
[106]
CHAPTER 6 Algae-Based Biologically Active Compounds
Weakly active against gram-positive and gramnegative bacteria, and blue-green algae
Structure
182
Sr. No.
7-Isopropyl-1,4dimethylazulene
C15H18
Obtained from essential oils, e.g., chamomile oil; found also in marine red algae and the gorgonians Euplexaura erecta and Alcyonium sp.
44
Isozeaxanthin; diketone
C40H52O2
Constit. of edible mushroom Cantharellus cinnabarinus, sea trout, salmon and brine shrimp, Corynebacterium michiganense also in green algae
45
Lutein
C40H56O2
46
Lycopene
C40H56
47
Cystoseirol-A
C27H36O4
Found in all higher plants, e.g., Mimosa invasiva, Cosmos caudatus, and also in microorganisms e.g., Staphylococcus aureus, green algae, Porphyra spp. Constit. of tomatoes and many other fruits; also occurs in bacteria and fungi; widely distributed in marine algae (red, green and brown) Constit. of brown algae Cystoseira mediterranea, Cystoseira stricta, and Cystoseira tamariscifolia
Antioxidant, inhibits lipid peroxidation; antiinflammatory agent, also used to treat gastrointestinal disorders; hepatoprotectant; immunodepressant; immunomodulatory and antiulcer agent Food coloring
[119]
O
[120]
O
Shows antitumor, antimutagenic and a wide range of antimicrobial activity; potentially useful for treating macular degeneration, antioxidant Used as food coloring
OH
[121]
HO
[122]
[123] O O O OH
48
Mutatochrome
C40H56O
[124]
183
Constit. of orange peel and blue-green algae; also in Calendula officinalis, Capsicum annuum (paprika), Delonix regia, and others
6.5 Biologically Active Compounds Extracted From Algae
43
Continued
Sr. No.
3,10(18)-Pachydictyadiene6,14,15-triol; (1a,5b,6b,11R,14R)-form
Molecular Formula C20H34O3
Biological Source
Biological Use
Structure
References
Isol. from brown algae D. dichotoma and Dictyota indica
[125] OH OH
HO
50
51
Polybromohydroxydiphenyl ethers; 2,30 ,4-tribromo-40 hydroxydiphenyl ether Prasinoxanthin
C12H7Br3O2
C40H56O4
Br
Isol. from Crustose coralline red algae Constit. of algae within Prasinophyceae
Br
Br O
Useful as a chemosystematic marker for algae
[126] OH
[127] O
OH
OH
OH
52
Sargassumketone
C15H18O10
Isol. from brown algae Sargassum kjellmanianum and Sargassum thunbergii
[128]
O
O HO
O O OH
O
O O
OH
53
Siphonaxanthin
C40H56O4
Caulerpa prolifera and other algae belonging to Prasinophyceae
Antiobesity
[129,130]
54
1,4,9,20-Tetraacetoxy1,3(20),6,10,14-phytapentaen19-al
C28H38O9
Halimeda spp. of green algae
Feeding deterrent to fish
[131] O
O O O
O
O
O
O
O
55
2,20 ,3,30 -Tetrabromo-4,40 ,5,50 tetrahydroxydiphenylmethane
C13H8Br4O4
OH
R. larix, R. confervoides, Polysiphonia nigrescens, and Polysiphonia brodiaci
[132] OH Br
Br
Br
OH
Br HO
CHAPTER 6 Algae-Based Biologically Active Compounds
49
Name
184
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d
56
Thyroxine; (S)-form
C15H11I4NO4
O
Thyromimetic, antihypercholesterolaemic
[133]
HO
NH2
I O I I
I OH
57
58
1,5,6-Trichloro-2(dichloromethyl)-6-methyl1,3,7-octatriene; (1Z,3E,5S,6R)-form
C10H11Cl5
9,11,15-Trihydroxyprosta5,13-dienoic acid; (5Z,8R,9S,11R,12R,13E,15S)form
C20H34O5
Isol. from red algae Plocamium cartilagineum and Plocamium coccineum and from mollusk Aplysia limacina Produced by a variety of marine algae and invertebrates, such as Phascolosoma japonica, Haliotis ovina, Crenomytilus grayanus, Modiolus difficilis, Stichopus japonicus, Distolasterias nipon, and Halocynthia aurantium Found in cyanobacteria and most marine algae
59
Zeaxanthin; (3R,30 R, all-E)-form
C40H56O2
60
Brasilenyne
C15H19ClO
Isol. from sea hare Aplysia brasiliana and algae L. nidifica
61
8-Bromo-1,5,6-trichloro-2(dichloromethyl)-6-methyl1,3,7-octatriene; (1Z,3E,5R*,6R*,7E)-form Telfairine
C10H10BrCl5
Constit. of red algae P. cartilagineum and Plocamium suhrii
Cl
[134] Cl
Cl Cl
Cl
OH
Abortifacient, oxytocic and smooth muscle stimulant
[135] OH
OH OH O
OH
[136]
HO
62
C10H14
Constit. of red alga Plocamium telfairia
Shows antifeedant activity
[137]
Cl
Cl
[138,139]
Br Cl Cl
Br
Insecticidal
Cl
[140]
Cl
185
H3C Cl
6.5 Biologically Active Compounds Extracted From Algae
Heterochordaria abietina, Undaria pinnatifida, Sargassum thunbergii, Polysiphonia urceolata, Dendrodoa grossularia, Porphyra umbilicalis, and Enteromorpha intestinalis
Cl CH3
Continued
186
Table 6.4 Terpenes and Terpenoids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
63
Sargatriol
C27H38O4
Biological Source
Biological Use
Structure
Constit. of brown alga Sargassum tortile
References [141]
HO OH OH OH
64
Methoxybifurcarenone
C28H40O5
Constit. of brown alga Cystoseira tamariscifolia
65
Astaxanthin
C40H52O4
Constit. of Haematococcus pluvialis
66
4-Bromophenol
C6H5BrO
Marine fish, mollusks, and algae
67
Geosmin
Constit., constituents; Isol., isolated.
C12H22O
Produced by Streptomyces spp. and blue-green algae
[142]
Antioxidant
[143]
OH
[101]
Br
Implicated in off-flavor of shellfish, freshwater fish, drinking water, and some vegetables
HO
[144]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
Sr. No. 1
Name Phycocyanin
Molecular Formula
Biological Source Constit. of bluegreen algae
Biological Use Antioxidative and antiinflammatory
Structure H3C H3C H3C O
2
Phycoerythrin
Constit. of bluegreen algae
N H
H3 C
4
Phycoerythrocyanin
Constit. of bluegreen algae Constit. of bluegreen algae
COO- COO
H3C
[145]
[145] H
N H
N H
N H
O
N/A
[145] SH H
H3C
COO- COO
H
H O
Constit., constituents.
CH3
N O H
H N H
CH3
N
SH H
H
Allophycocyanin
CH3
N H
H3 C
O
3
References
COOHCOOH
N H
[145] H
N H
N H
N H
O
6.5 Biologically Active Compounds Extracted From Algae
Table 6.5 Phycobiliproteins: Biologically Active Constituents Extracted From Algae
187
188
Table 6.6 Sterols: Biologically Active Constituents Extracted From Algae
1
Name Cholesta-5,23-diene3,25-diol; (3b,23E)-form
Molecular Formula C27H44O2
Biological Source
Biological Use
Structure
References
Constit. of red algae Liagora distenta and Scinaia furcellata
HO
[148]
Constit. of red algae L. distenta and S. furcellata
HO
Isol. from brown alga Rhodymenia palmata, red algae Asparagopsis armata, Rissoella verruculosa, and the tetraspora Falkenbergia rufolanosa Constit. of Funtumia latifolia; found in red algae R. palmata and Halosaccion ramentaceum and Patinopecten yessoensis Constit. of Mandevilla pentlandiana and the marine algae Bryopteris pennata and Scinaia fascicularis
HO
OH
2
Cholesta-5,23-diene3,25-diol; (3b,23Z)-form
C27H44O2
[148]
OH
3
Cholesta-5,25-diene3,24-diol; (3b,24S)-form
C27H44O2
4
Cholesta-5,24-dien-3ol; 3b-form
C27H44O
5
Cholesta-5,20,24-trien3-ol; 3b-form
C27H42O
[149]
HO
HO
[150,151]
HO
[152,153]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
6
8
Ergosta-5,24(28)-dien3-ol; 3b-form
Ergosta-5,25-dien-3-ol; (3b,24R)-form
C30H52O
C28H46O
C28H46O
9
Ergosta-5,7,22,25tetraen-3-ol; (3b,22E,24S)-form
C28H42O
10
24Hydroperoxystigmasta5,28-dien-3-ol; (3b,24x)form
C29H48O3
Constit. of Gonyaulax tamarensis, Styela plicata, Sarcophyton glaucum, Holothuria scabra, Pseudostichopus trachus, Synapta maculate, and dinoflagellate sediments Constit. of many marine organisms, such as Eupentacta fraudatrix, Holothuria nobilis, S. maculata, Echinus esculentus, Echinocardium cordatum, Antedon bifida, and Ophiocomina nigra; major sterol of green algae Constit. of Verongia cauliformis, Jaspis stellifera, and Chrysophyte unicellular algae Isol. from the algae Dictylostelium discoideum, Prototheca wickerhamii, and the sponge Ciocalypta sp.
Occurs in dinoflagellates and rarely in other algae, and has been used as a marker of dinoflagellate contribution to organic sediments
Obtained from tunicates Phallusia mamillata, Ciona intestinalis, Turbinaria conoides, and Padina pavonica as well as brown algae
Shows cytotoxic activity
[154]
HO
[155,156]
Cytotoxic HO
[157]
HO
[158]
HO
[159,160]
6.5 Biologically Active Compounds Extracted From Algae
7
4,23-Dimethylergost22-en-3-ol; (3b,4a,5a,22E,24R)form
OH
189
O OH
Continued
Sr. No.
Name
Molecular Formula C29H46O
12
Stigmasta-5,28-diene3,24-diol; (3b,24x)-form
C29H48O2
13
Stigmasta-5,22-dien-3ol; (3b,22E,24R)-form
C29H48O
14
15
Stigmasta-5,24(28)dien-3-ol; (3b,24(28)E)form
Stigmasta-5,24(28)dien-3-ol; (3b,24(28)Z)form
C29H48O
C29H48O
Biological Source Constit. of red algae and Haliclona longleyi; also from green alga Monostroma nitidum Constit. of Sargassum ringgoldianum also from green algae Ulva rigida and Ulva fasciata Constit. of sponges, e.g., Cliona celata, Spheciospongia vesparia, and Haliclona variabilis, green algae Chlorella spp., Ochromonas malhamensis, and clam P. yessoensis Characteristic sterol of brown algae Fucus vesiculosus; also present in Sargassum tortile, Cystoseira sp., Bifurcaria sp., and a marine unicellular alga; also in sponges Stelletta clarella, Tethya aurantia, Lissodendoryx noxiosa, Haliclona permollis, and other Haliclona spp. Major sterol of Callyspongia diffusa and other sponges and some green algae; also found in marine unicellular alga
Biological Use
Structure
References [161] OH
HO
[162,163]
HO
[164,165]
HO
[161]
HO
[161]
HO
CHAPTER 6 Algae-Based Biologically Active Compounds
25-Methylergosta5,7,22-trien-3-ol; (3b,22E,24x)-form
11
190
Table 6.6 Sterols: Biologically Active Constituents Extracted From Algaedcont’d
16
C29H46O
17
Stigmasta-7,9(11),22trien-3-ol; (3b,22E,24S)form
C29H46O
18
Stigmast-5-en-3-ol; (3b,24S)-form
C29H50O
Constit. of Corbicula leana and green algae and higher plants, also isol. from the Phellodendron sp. Constit. of Haloxylon recurvum and marine algae
[166] OH
[167]
HO
Constit., constituents; Isol., isolated.
Constit. of S. vesparia, C. celata, T. aurantia, liverworts, green algae Chaetomorpha aurea, Caulerpa prolifera, Bryopsis plumosa, and Udotea petiolata
[168]
HO
6.5 Biologically Active Compounds Extracted From Algae
Stigmasta-5,7,22-trien3-ol; (3b,24R)-form
191
192
CHAPTER 6 Algae-Based Biologically Active Compounds
generally of the order of 50,000e1,000,000 Da [169]. The details of these compounds are briefly summarized in Table 6.7.
6.5.9 ALKALOIDS The definition of the term alkaloid is not a simple one and is in many cases a source of academic controversy. They constitute a major class of natural products. Alkaloids are nitrogen-containing compounds derived from plants and animals. On the basis of structure, alkaloids are classified into three types [173]. • • •
True alkaloids Protoalkaloids Pseudoalkaloids The details of these compounds are briefly summarized in Table 6.8.
6.5.10 AMINO ACIDS Amino Acids (AA) are defined as organic substances that contain both amino and acid groups. Some amino acid contain two carboxyl groups and some contain two amino groups [196]. The details of these compounds are briefly summarized in Table 6.9.
6.5.11 FATTY ACIDS Fatty acids are the carboxylic acids derived from vegetable oils and animal fats. These are composed of a chain of alkyl groups usually containing an even number (4e22) of carbon atoms and are characterized by a terminal carboxylic group (eCOOH). Their general formula is CH3 (CH2)x COOH. They can be saturated or unsaturated [218]. The details of these compounds have been briefly summarized in Table 6.10.
6.5.12 HYDROCARBONS Hydrocarbons are the compounds composed of only carbon and hydrogen. Alkanes are saturated hyrocarbons, that is, they contain only carbonecarbon single bonds. Those containing one or more carbonecarbon double bonds, triple bonds, or benzene rings are classified as unsaturated hydrocarbon [71]. The details of these compounds are briefly summarized in Table 6.11.
6.5.13 OXYGEN HETEROCYCLES Heterocycles are defined as cyclic molecules that contain one or more heteroatoms in a ring. A heteroatom is an atom other than carbon; common heteroatoms are oxygen, nitrogen, and sulfur. Oxygen heterocycles are compounds that contain
Sr. No. 1
Name Poly-3-hydroxybutyrate (PH3B)
Molecular Formula
Biological Source Blue-green alga Chlorogloea fritschii
Biological Use
Structure CH3
References O
[170]
H O
OH
n
2
Poly(3-hydroxybutyrate-co3-hydroxyvalerate) PHBV
3
Polyhydroxy valerate (PHV)
Produced by the cyanobacterium Nostoc muscorum Agardh Blue-green algae Osxillatoris limosa
[171]
CH2CH3
O
[172]
O n
6.5 Biologically Active Compounds Extracted From Algae
Table 6.7 Polyhydroxyalkonates: Biologically Active Constituents Extracted From Algae
193
Sr. No.
2
Ambiguine-B isonitrile; Deoxy
Ambiguine-D isonitrile
Molecular Formula C26H31ClN2
C26H29ClN2O3
Biological Source
Biological Use
Structure
References
Cl
Blue-green algae Fischerella ambigua, Hapalosiphon hibernicus, and Westiellopsis prolifica
[174,175] N
N H Cl
Blue-green algae F. ambigua and W. prolifica
[174,175]
OH
N
OH
O
N
3
Ambiguine-E isonitrile
C26H29ClN2O2
Cl
F. ambigua, H. hibernicus, and W. prolifica
[174,175]
OH
N
O
NH
4
Ambiguine-G nitrile
C26H27ClN2
Cl
F. ambigua and Hapalosiphon delicatulus
[176] N
NH
5
Biliverdin; 15,16Dihydro
C33H36N4O6
Cyanobacteria and red algae, including Cyanidium caldarium
HO
Chlorophyll d
C54H70MgN4O6
Red algae
NH
NH N
6
[177]
O O
O
HN
HO
O
[14]
CHAPTER 6 Algae-Based Biologically Active Compounds
1
Name
194
Table 6.8 Alkaloids: Biologically Active Constituents Extracted From Algae
7
8
10
11
C10H9Br2NS2
5,12-Dihydrocycloocta [1,2-b:5,6-b0 ]diindole6,13-dicarboxylic acid, Di-Me ester
C24H18N2O4
5,6-Dihydro-3-[2-(1Hindol-3-yl)-2-oxoethyl]2(1H)-pyridinone,
Hordenine
1H-Indole-3-acetic acid
C15H14N2O2
C10H15NO
C10H9NO2
Isol. from red algae Laurencia brongniartii and Laurencia grevilleana Green algae Caulerpa serrulata, Caulerpa racemosa, Caulerpa sertularioides, Caulerpa taxifolia, Caulerpa cuppresoides, Caulerpa scalpelliformis, Caloglossa leprieurii, and Laurencia majuscule Isol. from an algaeinfested Caribbean sponge Halichondria melanodocia Anhalonium fissuratum, Hordeum vulgare; also present in the Amaryllidaceae, Gramineae, Leguminosae, and algae and fungi including marine alga Phyllophora nervosa
[178]
S S N H
Br
O
Plant growth regulator, phycotoxin, vermifuge
N H O
O H N
[179,180]
O
H N
[181]
O O HN
Diuretic, disinfectant, antihypotensive (in large doses) agent; used for treatment of dysentery; feeding repellant for grasshoppers; shows similar actions to 2(methylamino)-1phenyl-1-propanol Plant growth hormone (auxin); involved in root development; phytotoxic agent
[182]
N
OH
O HN
OH
[183]
195
Isol. from the marine alga Undaria pinnatifida, also in bacteria, yeasts, and fungi
Br
6.5 Biologically Active Compounds Extracted From Algae
9
4,6-Dibromo-2,3bis(methylthio)-1Hindole
Continued
196
Table 6.8 Alkaloids: Biologically Active Constituents Extracted From Algaedcont’d
12
13
Name
Molecular Formula
1H-Indole-3-carboxylic acid
C9H7NO2
1H-Indole-3-ethanol; O-b-D-Glucopyranoside
C16H21NO6
Biological Source
Biological Use
Structure
References
OH
Present in apple, garden pea, Brassica spp., and the marine algae U. pinnatifida and Botryocladia leptopoda Isol. from numerous plant and algae
[183]
O
NH
H N
HO
OH OH
[184]
O
HO
O
14
10 -Methylzeatin; (R)form, 2-Hydroxy
C11H15N5O2
15
2-Phenylethylamine
C8H11N
16
Phycocyanobilin
C33H38N4O6
Produced by Alternaria brassicae and isol. from marine green algae
Shows cytokinin activity; plant growth stimulator
Acacia spp., Crataegus spp.; also present in animal tissues, some algae, fungi and cacti (Leguminosae, Rosaceae, Cactaceae). Metab. of Prosopis alba Phormidium luridum, Synechococcus lividus, and Plectonema boryanum; also present in red algae
Shows DNA binding activity. Monoamine oxidase inhibitor
N
H N
[185]
NH N
N
OH OH
NH2
HO
O
H N
[186]
O
[187] H N N
HO O
O NH
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
17
Phycoerythrobilin
C33H38N4O6
Blue-green algae as well as most red algae
O
N
H N
NH O
20
C6H9NO4
Saxitoxin; N1-Hydroxy
C10H17N7O5
2,3,5,6-Tetrabromo1H-indole
C8H3Br4N
Thallusin
C25H31NO7
Constit. of Mediterranean red algae Chondria coerulescens, Chondria dasiphylla, and Ceramium rubrum Found in shellfish, marine algae, and other organisms incl. Gonyaulax tamarensis, Saxidomus giganteus, Vibrio sp., Pyrodinium sp. L. brongniartii and Laurencia similis
H N
O
[189]
O
O
6.5 Biologically Active Compounds Extracted From Algae
19
2,4Pyrrolidinedicarboxylic acid; (2S,4R)-form
[188]
O
NH
18
OH
OH
OH OH
Neurotoxic neuromuscular blocker
NH HN
O O
NH2 HO
N
NH
[190] OH OH
N
HN
H N
Br
[191] Br
Br Br
21
Isol. from a marine bacterium Cytophaga sp. YM2-23 obt. from a Monostroma sp.
O
Morphogenesis inducer in algae
OH N
OH OH O
22
C21H21ClN2O2S
Blue-green algae Hapalosiphon welwitschii and Westiella intricata
O
Cl
N S
[193]
197
Welwitindolinone-B isothiocyanate
[192] O
O O N H
Continued
198
Sr. No.
Name
Molecular Formula
23
Zeatin; (E)-form
C10H13N5O
24
Adenosine diphosphate glucose
Constit., constituents; Isol., isolated.
C16H25N5O15P2
Biological Source
Biological Use
Isol. from sweet corn Zea mays and numerous other plants; also from algae, bacteria, and basidiomycetes Present in ripening cereal grains; also obt. from algal cells
Induces cell division; most effective of all known natural cytokinins; nematicide Serves as the glycosyl donor for formation of bacterial glycogen, amylose in green algae, and amylopectin in higher plants
Structure N
H N
References [194]
NH N
N OH
OH
HO
[195] O
HO
O HO P O
HO
N
N
O
O
H2N N
OH P O O
N HO
OH
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.8 Alkaloids: Biologically Active Constituents Extracted From Algaedcont’d
Table 6.9 Amino Acids: Biologically Active Constituents Extracted From Algae Sr. No. 1
Name 3-Aminopropanoic acid
Molecular Formula C3H7NO2
N2-Arginylglutamine; LL-form
C11H22N6O4
3
Chondrine; (1S,3S)form
C5H9NO3S
Gigartinine; (S)-form
C7H15N5O3
4
5
Gongrine
C6H12N4O3
Widely distributed in plants including algae, fungi, and many higher plants Isol. from Euglena gracilis and from the green algae Cladophora spp., Enteromorpha linza, and Ulva pertusa Red alga Chondria crassicaulis, brown alga Undaria pinnatifida Constit. of many spp. of red algae, e.g., Gymnogongrus flabelliformis, Gelidium amansii, Grateloupia livida, Grateloupia filicina, Polyopes polyideoides, Carpopeltis flabellata, Hypnea japonica, and Gracilaria textorii Isol. from red algae G. flabelliformis and G. filicina
Biological Use
Structure
References
Catalyst for Knoevenagel condensations. Used for synthesis of Pantothenic acid and derivatives
HO
[197] O
NH2
[198,199]
O
OH
[200,201]
NH S
O
H N
O
NH2
[202]
NH NH H2N O OH
H N
O
NH2
[203,204]
NH NH HO O
6
Methionine sulfoxide; (S)C(R)S-form
C5H11NO3S
O H2N
[205] OH
O S
Continued
199
Isol. from various red algae incl. Amphiroa beauvoisii and Grateloupia proteus
6.5 Biologically Active Compounds Extracted From Algae
2
Biological Source
Sr. No.
8
9
10
11
12
Methionine sulfoxide; (S)C(R)S-form, N-Me
N-(2-Sulfoethyl)alanine; (R)-form
Molecular Formula C6H13NO3S
C5H11NO5S
1,2,3,6-Tetrahydro-2pyridinecarboxylic acid; (S)-form
C6H9NO2
N-Trimethyllysine betaine; (S)-form
C9H20N2O2
Citrulline; (S)-form
C6H13N3O3
Domoic acid
C15H21NO6
Biological Source Isol. from various red algae incl. Centroceras clavulatum, Grateloupia doryphora, and Gelidium latifolium Isol. from algae Chondrus ocellatus and Rhodoglossum japonicum Present in Baikiaea plurijuga, Caesalpinia tinctoria, red algae also in Russula subnigricans Green alga Enteromorpha intestinalis, brown algae Laminaria angustata, and Heterochordaria abietina; also from the seaweed Petalonia fascia Occurs in the watermelon Citrullus vulgaris, green alga E. intestinalis, and red alga G. filicina; widely distributed in Cucurbitaceae and fungi Constit. of red algae Chondria armata and Alsidium corallinum
Biological Use
Structure
References
O
H N
[205,206] OH
O S
H N HO
Neurotransmission inhibitor
Intermediate in biosynthesis of carnitine and g-butyrobetaine; cell proliferation stimulant. Antihypertensive and hypocholesterolemic agent Diuretic agent; used as arginine substitute in the treatment of inborn errors of urea synthesis, carbamyl phosphate synthetase and ornithine transcarbamylase deficiency Ionotropic glutamate (kainate) receptor agonist; neurotoxin. amnesic shellfish poison; vermifuge, insecticide
OH S O O
O
O
OH
[207,208]
[205,209]
HN
NH 2 N+
-
O
NH2
HN H2N
O HO
H N
[205]
O
OH O OH
[211]
O
OH O
[210]
O
CHAPTER 6 Algae-Based Biologically Active Compounds
7
Name
200
Table 6.9 Amino Acids: Biologically Active Constituents Extracted From Algaedcont’d
13
14
16
C10H15NO4
2,5Pyrrolidinedicarboxylic acid; S,5S)-form
C6H9NO4
4-Hydroxy-2pyrrolidinecarboxylic acid; (2R,4R)-form, NMe
C6H11NO3
2-Aminoethanesulfonic acid
C2H7NO3S
Constit. of red algae Alsidium helminthochorton, C. clavulatum, and Digenea simplex Reported from red algae Schizymenia dubyi and Haematocelis rubens Constit. of Capsicum annuum, Copaifera spp., Croton gubougia, Dalbergia sympathetica, Erythroxylum argentinum, Toddalia aculeate, and Afrormosia elata; also from red alga Chondria coerulescens and other red algae Occurs in animal tissues, bacteria, sponges, and red algae, e.g., isol. from Macrocallista nimbosa, Turbo stenogyrus, Calyx nicaeensis, Geodia gigas, Mytilus edulis. Also from green algae, e.g., Caulerpa okamurai, Caulerpa racemosa, Chlorodesmis comosa, Codium adherens, Codium fragile, and E. linza; and from higher plants, e.g., leguminous seedlings
O
Glutamate receptor agonist; neurotoxin, formerly used as an anthelmintic agent
[205]
OH OH N H
O
O
[205]
H N
HO
O
6.5 Biologically Active Compounds Extracted From Algae
15
Kainic acid
OH
N
O HO
[212]
OH
HO
Used as an adjunct in treatment of hypercholesterolaemia; metabolic regulator
O
O S
[213] NH2
201
Continued
202
Sr. No. 17 18
19
20
21
Molecular Formula
Biological Source
2-Aminoethanesulfonic acid; N,N-Di-Me
C4H11NO3S
Furcellaria fastigiata
2-Aminoethanesulfonic acid; N-Me
C3H9NO3S
2-Amino-3-hydroxy-1propanesulfonic acid; (S)-form
C3H9NO4S
Name
3-Amino-1propanesulfonic acid
2,5-Diaminopentanoic acid; (S)-form
Constit., constituents; Isol., isolated.
Biological Use
Structure O
O
[214]
S
N
HO
C3H9NO3S
C5H12N2O2
Red alga Ptilota pectinata and green alga C. comosa. Isol. from brown (e.g., Hijikia fusiforme) and green (U. pertusa, E. linza) algae. Also from diatoms, e.g., Navicula pelliculosa and starfish Asterina pectinifera Constit. of marine red algae, e.g., G. livida and from green alga Cladophora densa
Isol. from green algae Codium decorticatum, E. intestinalis, and Ulva lactuca
O
References
O S
[215] N H
HO
O HO S O
[59] NH2 OH
Inhibits amyloid A fibril formation and deposition; used in the treatment of Alzheimer disease and cerebral amyloid angiopathy Used in treatment of hyperammonemia and liver disorders
NH2
HO O S O
H2N HO
[216]
NH2 O
[217]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.9 Amino Acids: Biologically Active Constituents Extracted From Algaedcont’d
Table 6.10 Fatty Acids: Biologically Active Constituents Extracted From Algae Sr. No. 1
3
4
Molecular Formula
3-Bromo-2-heptenoic acid; (E)form
C7H11BrO2
(2-Carboxyethyl) dimethylsulfonium(1þ)
C5H11O2S1þ
13-(2-Cyclopentenyl)tridecanoic acid; x-form, 20 ,30 -dihydro
C18H34O2
11-(2-Cyclopentenyl) undecanoic acid; (þ)-form, 20 ,30 -dihydro
C16H30O2
Biological Source Constit. of red algae Bonnemaisonia hamifera and Bonnemaisonia nootkana Isol. from green and red algae, e.g., Enteromorpha intestinalis, Ulva lactuca; also from Spartina anglica Constit. of Hydnocarpus anthelmintica and various red algae of Solieriaceae
Biological Use
Structure
References
O Br
Biological precursor of Dimethyl sulphide; fish feeding stimulant
[219]
OH
S+
[220]
OH O
[221]
O HO
Constit. of H. anthelmintica and various red algae of Solieriaceae
[221]
O HO
5
6
2-(Dibromomethylene)octanoic acid
5,7,9,14,17-Eicosapentaenoic acid; (5E,7E,9E,14Z,17Z)-form
C9H14Br2O2
C20H30O2
Isol. from red algae Bonnemaisonia spp. Isol. from red algae Murraya periclados and Ptilota filicina
Br
[222]
Br
O HO
O OH
[223,224]
Continued
6.5 Biologically Active Compounds Extracted From Algae
2
Name
203
204
Table 6.10 Fatty Acids: Biologically Active Constituents Extracted From Algaedcont’d Name
Molecular Formula
5,8,11,14,17-Eicosapentaenoic acid; (all-Z)-form
C20H30O2
8
7,10,13-Hexadecatrienoic acid; (Z,Z,Z)-form
C16H26O2
9
3-Hexadecenoic acid; (E)-form
C16H30O2
10
2-Oxohexadecanoic acid
C16H30O3
7
11
12
12,13-Dihydroxy-5,8,10,14,17eicosapentaenoic acid; (5Z,8Z,10E,12R,13S,14Z,17Z)form
C20H30O4
13-Hydroxy-5,8,11,14,17eicosapentaenoic acid; (all-Z)form, Et ester
C22H34O3
Biological Source Present in fish oils, in animal phospholipids, and constit of various red algae
Present in a wide variety of angiosperm leaves and green algae; isol. from the sponge Dysidea fragilis Constit. of spinach leaves, red clover, Grindelia oxylepis, and Helenium bigelovii; also isol. from algae Constit. of algae Porphyra sp. and Ulva pertusa Constit. of red algae Farlowia mollis and Gracilariopsis lemaneiformis Isol. from a mixture of algae Lithothamnion calcareum and Lithothamnion corallioides
Biological Use Nutriceutical with antioxidation props; precursor of PG3 series of prostaglandins; platelet aggregation inhibitor; allelopathic agent
Structure
References
O
[225] OH
HO
HO
O
[226]
O
[227]
HO
O
[228]
O
OH
[229]
OH
O OH
O O
OH
[230]
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
13
15
16
C20H32O3
8-Hydroxy-13-oxo-5,9,11,14eicosatetraenoic acid; (5Z,8x,9E,11E,14E)-form
C20H30O4
2-Propenoic acid
C3H4O2
13-Octadecenoic acid; (Z)-form
Constit., constituents; Isol., isolated.
Found in red algae Murrayella periclados and Platysiphonia miniata, and sponge Echinochalina mollis Isol. from the algae Lithothamnion spp.
Immunohormone; cell growth inhibitor; proinflammatory agent; toxic to brine shrimp
OH
[224]
O
HO
HO O
[230]
O OH
C18H34O2
Found in green algae; produced by Phaeocystis sp., Phaeocystis pouchetii, Enteromorpha sp., Ulva sp., Codium sp., Patinopecten yessonensis, and Protogonyaulax sp. Constit. of algae, bacteria, fish; also found in various plant spp.; isol. from Haliclona cinerea
OH
[226]
O
HO
O
[231]
6.5 Biologically Active Compounds Extracted From Algae
14
12-Hydroxy-5,8,10,14eicosatetraenoic acid; (5Z,8Z,10E,12S,14Z)-form
205
206
Table 6.11 Hydrocarbons: Biologically Active Constituents Extracted From Algae
1
2
3
Name Bromochloromethane
Bromodichloromethane
Bromoiodomethane
Molecular Formula CH2BrCl
CHBrCl2
CH2BrI
4
Bromomethane
CH3Br
5
Carbon tetrabromide
CBr4
6
Carbon tetrachloride
CCl4
Biological Source Isol. from several marine algae Isol. from several marine algae Isol. from several marine algae Isol. from various marine sources incl. giant kelp and ice algae.
Isol. from various marine algae including Asparagopsis taxiformis Isol. from several plants and marine algae
Biological Use
Structure
References
Intermediate for organic synthesis, fire extinguishant Source of dichlorocarbene on treatment with base
Cl
[232] Br
Cl
Br
[232,233]
Cl
Br
[232,234] I
Principally used as an insecticidal and nemacidal fumigant, especially for soil and agricultural produce
Br
[232,234]
Br Br
Br
[232,234]
Br
Cl
Anthelmintic Cl
[232,234] Cl
Cl
7
8
9
10
Chloroform
Chloroiodomethane
Dibromochloromethane
Dibromoiodomethane
CHCl3
CH2C11
CHBr2Cl
CHBr2I
Found in various plants and algae
Isol. from phytoplankton and various marine algae Isol. from several marine algae including A. taxiformis Isol. from several marine algae including A. taxiformis
Formerly used as anesthetic. Topical remedy for Herpes simplex sores Versatile organic synthon. Commercially available Source of bromochlorocarbene in the presence of base and crown ether
Cl Cl
[232,234] Cl
I
[232,234]
Cl
Br Cl
[232,234] Br
Br I
[232,234] Br
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
11
12
Dichloromethane
Diiodomethane
CH2Br2
CH2Cl2
CH2I2
14
Ethylamine
C2H7N
15
3,6,9,12,15,18Heneicosahexaene; (allZ)-form
C21H32
16
C21H34
17
3,6,9,12,15Heneicosapentaene; (all-Z)-form 1-Hexacosene
C26H52
18
1-Iodobutane
C4H9I
Isol. from various marine algae including red alga A. taxiformis Found in various plants and algae and in volcanic gases
Br
Widely used solvent used in coffee decaffeination. Component of paint removers. Blowing agent in foams. Can replace formaldehyde as reagent for Mannich reagents
Cl
[232,234] Br
[232] Cl
I
[234] I
Used in manufacture of resins, rubber, herbicides, etc.
H 2N
[235]
[236]
[237,238]
[239]
Used to esterify fatty acids for GC analysis
[232] I
Continued
207
Isol. from various marine algae Produced by marine algae, Clostridium spp., Candida albicans, Brevibacterium linens and Streptococcus lactis Isol. from marine algae and plankton, e.g., Rhizosolenia setigera and Skeletonema costatum Constit. of Polytrichum commune and benthic green algae Constit. of Acanthopanax giraldii, Aralia elata, Hippophae rhamnoides and various algae incl. Chlorella sp. Isol. from several marine algae
Solvent, reagent for organic synthesis
6.5 Biologically Active Compounds Extracted From Algae
13
Dibromomethane
208
Sr. No.
Name
Molecular Formula
19
Iodoethane
C2H5I
20
Iodomethane
CH3I
21
7-Methylheptadecane
C18H38
22
3,6,9,12,15Nonadecapentaene; (allZ)-form
C19H30
23
Pentadecane
C15H32
24
3,6,9,12Pentadecatetraen-1yne; (3E,6Z,9Z,12Z)form
C15H20
25
3,6,9-Pentadecatrien-1yne; (3E,6Z,9Z)-form
C15H22
Biological Source
Biological Use
Structure
References
Isol. from several marine algae Isol. from marine algae and giant kelp.
Used to esterify fatty acids for GC analysis Methylating agent, Soil fumigant, insecticide, acaracide, rodenticide and fungicide
I
[232]
I
[232]
Isol. from various bluegreen algae including Anabaena sp. and Nostoc sp. Found in marine benthic algae
[240]
Blue-green algae Oscillatoria splendida, Oscillatoria amoena, Oscillatoria geminate, Rumex japonicas, Vallisneria denseserrulate, and Aphanizomenon sp. Isol. from Laurencia okamurai
[238]
Constit. of L. okamurai
[238]
Possible precursor of a wide range of C-15halogenated cyclic ethers found in marine red algae Possible precursor of a wide range of C-15halogenated cyclic ethers found in marine red algae
[241]
[242]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.11 Hydrocarbons: Biologically Active Constituents Extracted From Algaedcont’d
26
Tribromomethane
CHBr3
1,3,5,8Undecatetraene; (3E,5Z,8Z)-form
C11H16
28
1,3,5-Undecatriene; (3E,5Z)-form
C11H18
Constit., constituents; Isol., isolated.
Antitussive; sedative, solvent for waxes, greases, and oils Smelling principle of the gametes of brown algae Spermatochnus paradoxus; sperm attractant of the marine brown alga Ascophyllum nodosum
Br Br
[243,244] Br
[245,246]
[247]
6.5 Biologically Active Compounds Extracted From Algae
27
Constit. of red algae Asparagopsis spp. and Falkenbergia rufolanosa Constit. of the algae of the genera Dictyopteris, Dictyosiphon and Spermatochnus; also occurs in mandarin and tangerine oranges and pineapple Occurs in algae Cystophora siliquosa and Dictyopteris sp.; isol. from the fruit of Ananas comosus (pineapple)
209
210
CHAPTER 6 Algae-Based Biologically Active Compounds
oxygen as a heteroatom in the ring [248]. The details of these compounds are briefly summarized in Table 6.12.
6.5.14 ALCOHOLS Alcohol is a class of compound containing eOH (hydroxyl) group. Alcohols are important because they can be converted into other types of compounds, including alkenes, haloalkanes, aldehydes, ketones, carboxylic acids, and esters. Thus alcohols play a central role in the interconversion of organic functional groups [71]. The details of these compounds are briefly summarized in Table 6.13.
6.5.15 LIPIDS Lipids are a heterogeneous group of naturally occurring organic compounds, classified together on the basis of their common solubility properties. Lipids are insoluble in water but soluble in nonpolar, aprotic organic solvents [71]. The details of these compounds are briefly summarized in Table 6.14.
6.5.16 CARBONYL COMPOUNDS Carbonyl compounds contain a carbonyl group C]O in their molecules. Carbonyl group is the functional group of aldehyde and ketone and is one of the important functional groups in organic chemistry [71]. The details of these compounds are briefly summarized in Table 6.15.
6.5.17 OTHERS Various other compounds have also been isolated from different species of algae. The details of these compounds are briefly summarized in Table 6.16.
6.6 THERAPEUTIC APPLICATIONS OF ALGAE Scientists all across the world are trying to resolve the relationship between structure and therapeutic activities of algal-sulfated biopolymers. A spate intrigue has been observed to dab unexploited aquatic channels for the improvement of innovative therapeutics as algal cell wall polysaccharides and phytoconstituents have revealed a miraculous biological capital. The pharmacological properties of algae and their mode of action are reviewed as under.
6.6.1 ANTICOAGULANT ACTIVITY Anticoagulant properties were first discovered in the extracts of marine algae over 50 years ago. The major active compounds are a variety of sulfated polysaccharides,
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algae Sr. No.
Name
Molecular Formula
1
1,5-Anhydrofructose; D-form
C6H10O5
Biological Source
Biological Use
Exists in rat liver, fungi, and algae
Antioxidant
Constit. of Lilium spp., Euonymus europaeus, Capsicum annuum, and Chrysophyceae algae Isol. from Viola tricolor, Lonicera japonica, Delonix regia, and other plants; present in red algae Present in red algae
Potential nutriceutical
Structure O
3
HO
Auroxanthin
Auroxanthin; 3,30 -Dideoxy
C40H56O3
C40H56O4
C40H56O2
OH
[250]
O
OH
HO
[251] O HO
O
6.6 Therapeutic Applications of Algae
4
Antheraxanthin; (3S,30 R,5S,6R,9Z)-form
[249]
O OH
2
References
HO
[251] O O
5
6
Cystoseirol-A
1-O-(6-Deoxy-6sulfoglucopyranosyl)glycerol; a-D-form, 3-Hexadecanoyl
C27H36O4
C25H48O11S
[123] O O O OH
[252]
211
Constit. of brown algae Cystoseira mediterranea, Cystoseira stricta, and Cystoseira tamariscifolia Isol. from Anthocidaris crassispina, brown algae Sargassum thunbergii, and Sargassum wightii; and red alga Caulacanthus ustulatus
Continued
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algaedcont’d
7
Name
C20H32O3
8
1,6-Di-O-b-Dglucopyranosyl-D-mannitol
C18H34O16
9
2,3-Dihydroxypropanoic acid; (R)-form, 2-O-a-DMannopyranoside
C9H16O9
10
2,3-Dihydroxypropyl [5deoxy-5-(dimethylarsino)] ribofuranoside; As-Oxide
C10H21AsO7
Biological Source
Biological Use
Constit. of brown algae Dictyota pardarlis, f. pseudohamata A7749 and Dictyota divaricate Occurs in brown algae Fucus vesiculosus, Fucus spiralis, Pelvetia canaliculata, Laminaria cloustoni, and Desmarestia aculeata Isol. from red algae Alsidium, Chondria, Laurencia, Polysiphonia, Halopytis, Vidalia, and Digenea spp. Isol. from brown algae Laminaria japonica and Ecklonia radiata, giant clam Tridacna maxima and various freshwater mussels Anodonta anatina, Dreissena polymorpha, Unio pictorum and Unio tumidas
Antimalarial agent
Structure
References [253]
HO
O
O
[254]
[255]
HO
OH
[256] O
O
HO OH
As O
CHAPTER 6 Algae-Based Biologically Active Compounds
3,4:7,8-Diepoxy-12dolabellen-18-ol; (1R*,3R*,4S*,7R*,8R*,11R*)form
Molecular Formula
212
Sr. No.
11
5,6-Epoxy-5,6-dihydro-b,εcarotene-3,30 -diol
C40H56O3
12
11,12-Epoxy-10-hydroxy5,8,14-eicosatrienoic acid; (5Z,8Z,10S,11S,12S,14Z)form
C20H32O4
13
Flexixanthin; 20 -Hydroxy, 20 O-a-L-rhamnopyranoside
C46H64O8
14
Fucoxanthinol; 30 -Ac
C42H58O6
3-O-a-D-Galactopyranosyl-
C12H22O11
D-galactose
16
C9H18O8
Constit. of various marine red algae
Insulin release enhancer; active against grampositive bacteria; toxic to brine shrimp
[257]
O O
OH
HO
[258]
Antioxidant, antifouling agent
[136,259]
O O
OH HO O
O
[260,261]
HO HO
[205,262] HO O
213
1-OGalactopyranosylglycerol; a-D-(2R)-form
[251]
6.6 Therapeutic Applications of Algae
15
Isol. from a variety of higher plants and from algae Constit. of Murrayella periclados, and algae Platysiphonia miniata and Cottoniella filamentosa Isol. from bluegreen algae Oscillatoria limosa and Phormidium faveolarum Constit. of algae, Fucus virsoides, Polysiphonia nigrescens, Colpomenia peregrina, Phaeodactylum tricornutum, Ceramium rubrum, and Hijikia fusiformis Isol. from Aeodes ulvoidea and Pachymenia carnosa
OH O
HO OH
Continued
214
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algaedcont’d
17
18
Name 2-O-a-DGalactopyranosylglycerol
Mannuronic acid: D-form
Molecular Formula C9H18O8
C6H10O7
Biological Source Constit. of many red algae, such as Plocamium cartilagineum, Laurencia pinnatifida, Iridaea laminaroides, and Bacillus coagulans Macrocystis pyrifera
Biological Use The main reserve carbohydrate in most red algae; prob. intracellular osmotic regulator
Structure
[205,263]
HO
O
HO
O OH
HO OH
O
HO
OH
HO
O OH
OH
HO
O O HO
HO HO
1,3,6-Tribromo-8methoxydibenzofuran
C13H7Br3O2
Isol. from crustose coralline red algae
1-O-D-Glucopyranosyl-Dmannitol; b-form
C12H24O11
HO
OH
Stypoldione
C27H38O4
Constit. of algae Stypopodium zonale, Stypopodium flabelliforme, and mollusk Aplysia dactyomela
Ichtyotoxin, algicide, toxic to sea urchin eggs; phospholipase A-2 inhibitor, microtubule inhibitor
O OH
[126] Br
O OH
OH HO HO
21
OH
Br
O
Constit. of F. vesiculosus and other brown algae
O
OH
Br
20
[264]
OH
HO
HO
19
References
HO
[265]
OH O O
OH
OH
[266]
HO
O
O O
CHAPTER 6 Algae-Based Biologically Active Compounds
Sr. No.
b-D-Xylopyranosyl-(1/3)b-D-xylopyranosyl-(1/3)-Dxylose;
C15H26O13
23
Myxol; 20 -O-6-Deoxy-a-Lglucoside
C46H66O7
24
Neoxanthin; (all-E)-form
C40H56O4
25
Violaxanthin; (all-E)-form
C40H56O4
26
Glycerol 1,2-dialkanoates; glycerol 1,2-dioctanoate, 3O-(6-Deoxy-6-sulfo-a-Dglucopyranoside)
C41H78O12S
Constit. of the Penicillus dumetosus, Rhodymenia palmate, and several other green algae Isol. from Oscillatoria rubescens, Oscillatoria agardhii, Arthrospira spp., and Phormidium luridum Constit. of paprika, lucerne, maple, Valencia orange; also in green algae
[267]
Constit. of many plants including V. tricolor; found in brown and green algae Constit. of the Byrsonima crassifolia and the algae Gracilaria verrucosa and Sargassum parvivesiculosum
[269]
[109,268]
6.6 Therapeutic Applications of Algae
22
[269]
[270]
215
Continued
Table 6.12 Oxygen Heterocycles: Biologically Active Constituents Extracted From Algaedcont’d
27
Violaxanthin; (all-E)-form, Monodeoxy
Chitin
Molecular Formula C40H56O3
C8H13NO5
Biological Source Isol. from the algae of Xanthophyceae, Eriobotrya japonica, and Prunus persica Occurs in crustacea, most fungi, mycelial yeast, green algae, and some brown and red algae
Biological Use
Structure
References OH O
O
Antihemorrhagic; used as a wound healant
H2 P O H N
O
HO
[271] O
O
OH O
HN
2,3-Dihydroxypropyl [5deoxy-5-(dimethylarsino)] ribofuranoside; As-Oxide, O30 -sulfate
C10H21AsO10S
30
5-Methyl-2furancarboxaldehyde
C6H6O2
31
a,a-Trehalose
C12H22O11
Isol. from T. maxima and brown algae Sargassum lacerifolium and Hizikia fusiforme Isol. from brown algae and other plant sources Occurs in fungi, molds, ergot, algae, yeast, and many insects
OH
OH
O
29
[269]
PH2
OH O O HO S
O
[272]
O
O
As
HO
Flavoring ingredient
Probable energy reserve in many organisms and important cellular protectant in drought resistant organisms; associated with maintenance of the integrity of biological membranes in organisms subject to severe thermal stresses; marker for tubercuosis infection in vivo
OH
O
O
[273]
OH HO
[274]
OH O
OH
HO
O O OH
HO OH
O
CHAPTER 6 Algae-Based Biologically Active Compounds
28
Name
216
Sr. No.
Galactose; L-form
C6H12O6
Occurs in agar eagar, chagual gum, red algae, flax seed mucilage, and a snail galactan
33
Mannose; D-form
C6H12O6
Phytelephas macrocarpa, Orchidaceae, Phoenix canariensis, Amorphophallus konjac; they are proliferated by some red algae and yeasts; also occurs in trace amounts in apples and peaches
Constit., constituents; Isol., isolated.
[275]
Inexpensive starting material for chiral synthesis
[275]
6.6 Therapeutic Applications of Algae
32
217
218
Sr. No. 1
2
3
Name Erythritol
Molecular Formula C4H10O4
2-Methyl-1,2,3,4butanetetrol; (2R,3R)-form, 4phosphate
C5H13O7P
1-Deoxy-1(dimethylarsinoyl) ribitol; 5-O-sulfate
C7H17AsO8S
Biological Source Found in a variety of algae, lichens and fungi; produced by Protococcus vulgaris, Trentepohlia iolithus, and Aspergillus terreus Bacteria, algae, and plant chloroplasts
Biological Use Bulk sweetener with good taste props; also thickener, stabilizer, humectant, etc. in food, shows vasodilatory props The first pathway-specific intermediate in the methylerythritol phosphate route for biosynthesis of isoprenoid compounds in bacteria, algae, and plant chloroplasts
Structure
References
OH
[276]
OH OH
O HO
OH
[277]
O P OH
OH
HO OH
O As
Isol. from Chondria crassicaulis and other red algae
HO
[278]
OH
HO O
S O O OH
4
5
Talitol; D-form
Mannitol; D-form
C6H14O6
C6H14O6
Isol. from various brown algae including Himanthalia elongata and Notheia anomala Olive and plane trees; obtained from manna and seaweeds; obtained industrially from fructose
OH
HO
Energy reserve in brown algae Diagnostic aid (renal function determination); diuretic; tablet and capsule diluent
[279,280]
OH
HO
OH HO
OH OH
HO HO
OH HO
[276]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.13 Alcohols: Biologically Active Constituents Extracted From Algae
6
1,1,3,3Tetrabromo-2heptanol
C7H12Br4O
7
2-Nonen-1-ol
C9H18O
8
Glucitol; D-form
C6H14O6
10
1-Bromo-3-iodo2-propanol; (x)form D-glycero-Dmanno-heptitol
[222]
Br
Br
OH Br
Present in melon, cucumber, brown algae, nectarine, and prickly pear Present in algae, apples, pears, cherries, and apricots; also present in Sorbus and Crataegus spp.
C3H6BrIO
Present in red algae Asparagopsis taxiformis
C7H16O7
Occurs in mushroom Lactarius volemus, in primulae and in Escherichia coli; also in red algae
Constit., constituents; Isol., isolated.
Used in food flavoring
Used in manufacture of sorbose, propylene glycol, ascorbic acid, resins, plasticizers and as antifreeze mixtures with glycerol or glycol; tablet diluent, sweetening agent and humectant, other food uses; used in photometric detn. of Ru(VI) and Ru(VIII); in acid ebase titration of borate
OH
OH OH
HO HO
[281]
[280]
OH HO
Br
[282]
I OH
OH
[276]
OH OH
HO
HO
OH HO
6.6 Therapeutic Applications of Algae
9
Br
Constit. of red algae Bonnemaisonia spp.
219
220
Sr. No. 1
2
3
4
Name 1,2-Diacylglyceryl-3-(Ocarboxyhydroxymethyl) choline 1,2-Diacylglyceryl-O-20 (hydroxymethyl)-N,N,Ntrimethyl-b-alanine Ulvaline
Lactyltrimethylarsonium betaine
Isol., isolated.
Molecular Formula
Biological Source
Biological Use
Betaine lipid present in some plants and algae
Structure
HO
O
O
O
O
References -
[283] N
+
OH
Isol. from various marine algae C10H21NO5
C6H13AsO3
Isol. from the marine plant Monostroma nitidum and the mushroom Lampteromyces japonicus; isol. from numerous marine sources including algae and bryophytes Marine algae, e.g., Dunaliella tertiolecta; also in diatom Chaetoceros concavicornis and lobster Homarus americanus
HO
O OH
Shows hypocholesterolaemic activity
-
O
[283]
O
[284]
O
+
N
OH O
O
N O
O
HO As
OH
[285]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.14 Lipids: Biologically Active Constituents Extracted From Algae
Table 6.15 Carbonyl Compounds: Biologically Active Constituents Extracted From Algae Sr. No.
Name
Molecular Formula
Biological Source
1
1,1-Dibromo-3-iodo2-propanone
C3H3Br2IO
Red algae, Asparagopsis taxiformis, and Asparagopsis armata
2
1,3-Dibromo-2propanone
C3H4Br2O
3
8,11,14Heptadecatrienal; (allZ)-form
C17H28O
4
1-Bromo-2propanone Dibromoacetaldehyde
C3H5BrO
Constit. of the marine algae A. armata, A. taxiformis, and Falkenbergia rufolanosa Constit. of cucumber, tobacco, and wheat; also found in the algae Enteromorpha sp., Scytosiphon lomentaria, and Ulva pertusa Isol. from the algae A. taxiformis and F. rufolanosa Isol. from the algae A. taxiformis and F. rufolanosa Component of red algae A. taxiformis, A. armata, and tetrasporophyte F. rufolanosa Constit. of seaweed Dictyopteris plagiogramma, green algae Bryopsis pennata, Caulerpa prolifera, and Cymopolia barbata, and other marine algae
Biological Use
Structure
References
O Br
[234]
I Br
6
7
1,3-Dibromo-1-chloro2-propanone; (0004)-form 3-Hexyl-1,2-dithiepan5-one; (0003)-form
C2H2Br2O C3H3Br2ClO
C11H20OS2
Br
[234] Br
O
Br
O
[286,287]
O
[234]
Br
[234]
Br O
[234]
Br Br
Cl
[288] S S O
Continued
6.6 Therapeutic Applications of Algae
5
O
221
222
Sr. No.
Name
Molecular Formula
Biological Source
8
2-Tridecyl-2heptadecenal; (E)-form
C30H58O
Constit. of red algae Corallina mediterranea, Laurencia obtusa, Laurencia papillosa, and Laurencia undulata; also prod. by a marinederived Cladosporium sp.
9
1,1,3-Tribromo-3chloro-2-propanone
C3H2Br3ClO
Red algae A. taxiformis and F. rufolanosa
10
1,1,3-Tribromo-2propanone
C3H3Br3O
Constit. of red algae Asparagopsis spp. and F. rufolanosa
11
6,10,14-Trimethyl-2pentadecanone; (x)form
C18H36O
Present in marine organisms such as sponge Spheciospongia vagabunda, algae Caulerpa taxifolia, and Padina tetrastromatica, and crab Carcinus maenas
Biological Use
Structure
[289]
O Br
[234]
Br Br
Constit., constituents; Isol., isolated.
References
Cl
O
[234]
Br Br
Br O
[290]
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.15 Carbonyl Compounds: Biologically Active Constituents Extracted From Algaedcont’d
Table 6.16 Other Compounds Extracted From Algae Sr. No. 1
Name 2-Amino-6-(1,2-dihydroxypropyl)4(1H)-pteridinone; (10 R,20 R)-form
Molecular Formula
Biological Source
C9H11N5O3
Widely distributed in microorganisms, insects, algae, amphibian, and mammals; Found in urine Found in algae, lobsters, sharks, and dogfish
Growth factor
Appears to be a hormonal messenger involved in cyclic GMP regulation; vasodilator. Used in the prophylaxis of graft dysfunction in patients receiving allogenic kidney transplants Selective reducing agent; reagent for ortho-alkylation of aromatic amines; used with diborane as effective reducing agent for esters, amides, etc.
Arsenobetaine
C5H11AsO2
3
Carbon monoxide
CO
Produced in traces by algae and higher plants
4
Dimethyl sulfide
C 2H 6S
Isol. from green and red algae and higher plants
Structure
[291]
OH
HO
References
N N
O N
NH NH2
[292]
-
O+
C
S
[293]
6.6 Therapeutic Applications of Algae
2
Biological Use
[294]
Continued
223
224
Sr. No. 5
Name 1-Pentacosene4,6,8,10,12,14,16,18,20-nonol; (4S,6S,8S,10S,1214R,16R,18R)form, Nona-Me ether
Molecular Formula
Biological Source
C34H68O9
Isol. from the bluegreen algae Scytonema burmanicum and Scytonema mirabile
Biological Use
Structure
References [114]
O O O O O O O O O
6
3-(Dimethylarsinyl)propanoic acid
Isol., isolated.
C5H11AsO3
Found in lobster, dogfish, oyster, blue mussel, horse mussel, scallop, cod, brown algae Ascophyllum nodosum, and Fucus vesiculosus
O
[295]
As
OH
O
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.16 Other Compounds Extracted From Algaedcont’d
6.6 Therapeutic Applications of Algae
some of which are characterized as proteoglycans [296]. Thrombin and plasmin are the proteolytic enzymes required for the activation of enzymes in fibrinolytic and coagulation cascade (Fig. 6.1). The balance between both pathways is obligatory, otherwise strokes and heart attacks are obvious due to excessive bleeding or thrombosis. Deep vein thrombosis is the major cause of mortality in posttraumatic cases and promulgates in operated patients [298]. Anticoagulant therapy is very beneficial in such situations. The first report of algal polysaccharide as anticoagulant agent was published in 1936 when Chargaff and colleagues succeeded to isolate the esters of sulfuric acid and galactan from Iridae laminarioides having anticoagulant activity equal to 30 U/mg of heparin. Consequent analysis revealed carrageenan and agar having similar anticoagulant properties. Up till now, approximately 150 species belonging to red-brown, green, and microalgae have been used to isolate this heterogeneous sulfated biopolymer (Table 6.17). Sulfated biopolymer heparin has been used as an anticoagulant since past 50 years in posttraumatic patients [317]. Its anticoagulating effect is expressed by heparin cofactor-II and antithrombin potentiation, a major anticoagulating enzyme (Fig. 6.1). However, algal-sulfated polysaccharides are most extensively studied as anticoagulants, more extensive studies are needed to overcome side effects, i.e., thrombocytopenia. [297]. This side effect was overcome by synthesizing low molecular weight algal-sulfated polysaccharides [318]. Similar to the algal-sulfated polysaccharides (heparin), dermatan sulfate, in combination with chondroitin sulfate, is also clinically employed, but unfortunately is little potent due to its high molecular weight [27]. Fucoidan from Ecklonia kurome is found to be more potent due to low molecular weight fractionation and low sulfation [319]. It was also observed that branched fucans isolated from brown algae have direct effect while linear fucans isolated from echinoderms require some antithrombin molecules for their action [320].
FIGURE 6.1 Schematic presentation of antithrombotic activity: antithrombotic effect of sulfated polysaccharides; (A) activation of prothrombin versus inactivation of prothrombinase by treating with sulfated polysaccharides [297].
225
226
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.17 Major Sugar Molecules of Algal Polysaccharides (PSs) Exhibiting Anticoagulating and Antithrombotic Agents Species
Major Sugar
PS
References
Grateloupia indica Gigartina skottsbergii Nothogenia fastigiata Lomentaria catenata Schizymenia binderi Porphyra haitanensis Monostroma nitidum Lessoni avadosa Ecklonia cava Ascophyllum nodosum Ecklonia kurome Monostroma latissimum Ulva conglobata Codium cylindricum Codium pugniformis Codium fragile Dictyota cervicornis Caulerpa cupresoides E. cava
Galactose Galactose Mannose Galactose Galactose Galactose Rhamnose Fucose Fucose Fucose Fucose Rhamnose Rhamnose Galactose Glucose Arabinose Mannose, fucose Galactose Arabinose, galactose
sPS sPS EsPS Galactan Galactan sPS PS (sulfated) PS (sulfated) PS (sulfated) PS (sulfated) PS (sulfated) sPS sPS Galactan sPS Arabinans Rhamnose Galactan Aribanogalactan
[299] [300] [301] [302] [303] [304] [305] [306] [307] [308] [309] [310] [311] [312] [302] [313] [314] [315] [316]
6.6.2 ANTIVIRAL ACTIVITIES OF ALGAE-BASED BIOLOGICALLY ACTIVE COMPOUNDS The use of algal polysaccharides as antiviral agent is not new as it goes back more than 50 years when Gerber and his colleagues inhibited influenza-B virus and mumps in 1955 [321]. Later it was assumed that the antiviral effect of sulfated polysaccharides was due to electrostatic prevention of viral adherence to cell surface [322]. This gushed exploration of antiviral achievements of diverse-natured sulfated polysaccharides including polyanionic substances [323]. With the structural elucidation of algal polysaccharides, isolation of seaweed polysaccharides as antiviral agents was substantially increased due to their ability to affect the viral replication by a number of nonspecific mechanisms (Fig. 6.2) [324]. Cladosiphon okamuranus fucan inhibited DENV-2 (Dengue fever type-2) with BHK-21 cells, but had very little effect on other serotypes. Structural analysis of DENV-2 enveloped glycoprotein exhibits that arginine-323 close to heparin-binding site is censorious for fucan interaction [27]. In accordance with these findings, Talarico and colleagues published that sulfated biopolymer from two genera of red algae, i.e., carrageenan from Gymnogongrus griffithsiae and galactan from Cryptonemia crenulata completely impeded DENV-2, with less impedance on DENV-3 and DENV-4, while
6.6 Therapeutic Applications of Algae
FIGURE 6.2 Antiviral mode of action of sulfated polysaccharides: antiviral mode of action of sulfated polysaccharides [297]; (A) binding of pathogen with host cell; (B) neutralization of pathogen.
remained ineffective against DENV-1 in cell lines [325,326]. These biopolymers use the phenomenon of adsorption, only when added soon after infection, as no inhibition was observed when viral entry was avoided by transfection into the cells [327]. Inhibition of herpes simplex virus-1 and -2 (HSV-1, HSV-2) by sulfated biopolymers has become a hot issue these days [328,329]. Sulfated xylomannan of Sebdenia polydactyla exhibited high potency against HSV-1 due to high sulfation, and the potency is further increased by increasing sulfation [330]. Inhibition of different viral species (Table 6.18) by biopolymers of different algal species indicated that Table 6.18 Effect of Algal Sulfated Polysaccharides (PSs) on Different Virus Species Species
Virus Strain
EC50/ED50 (mg/mL)
Type of PS
References
Schizymenia pacifica Nothogenia Fastigiata Digenea simplex Pterocladia capillacea
HIV-1
7e14
Carrageenan
[331]
HIV-1
061e1.35
(Xylo)mannans
[332]
HIV
2.84
[333]
HSV-1
2.6e10
Gigartina skottsbergii Cryptopleura ramosa Salvia interrupta
HSV-1, HSV-2
>1
sp. noncharacterized Sulfated agarans and hybrid DLgalactans Carrageenan
HSV-1, HSV-2
1.6e4.2
[335]
HSV-1, HSV-2
1.5e36
Sulfated agarans Carrageenans
[334]
[335]
[329] Continued
227
228
CHAPTER 6 Algae-Based Biologically Active Compounds
Table 6.18 Effect of Algal Sulfated Polysaccharides (PSs) on Different Virus Speciesdcont’d Species
Virus Strain
EC50/ED50 (mg/mL)
Type of PS
References
Sulfated agarans Sulfated agarans
[336]
1 and 0.7 e6.6 Asparagopsis armata Porphyridium cruentum
Gyrodinium impudicum Rhodella reticulata
Monostroma latissinum Porphyridium sp.
HIV
40.2
African swine fever virus (ASFV); vaccinia virus (VACV); vesicular stomatitis virus (VSV) Encephalomyocarditis virus; influenza A virus (Flu-A) HSV-2; varicela zoster virus (VZV); murine sarcoma virus (MuSV124), and MuSV/ MuLV (murine eukemia virus) HSV-1, HCMV, HIV-1
12e56; 20e45
0.19e0.48
Hybrid DLgalactans
[309]
10e20; 8; 150 and 50
Sulfated agarans
[337]
3.7
Sulfated Rhamnans Extract
[338]
Extract
[340]
Fucans
[341]
0.5e1.9
Fucans
[338]
HSV-1, HCMV HIV-1
45.5
Fucans
[342]
HIV-1
49
Fucans
[302]
HSV-1, HSV-2
Cochlodinium polykrikoides
HIV-1, RSV, Inf A, Inf B
Pennisetum purpureum
Vaccinia virus VACV and VACV-GFP; ectromelia virus (ECTV) HSV-1
Leathesia difformis Sargassum horneri Fucus vesiculosus
[242]
1e5 (in vivo, 100); 0.7; 10 and 5 (RT50) 0.45e1.1 and 7.1e8.3; 2.0e3.0 and 0.8; 1.7; 4.52e21.6; 0.8e25.3 0.65
[339]
6.6 Therapeutic Applications of Algae
antiviral activity is greatly affected by degree of sulfation, arrangement of sulfate, composition of sugar moieties, stereochemistry, or its molecular weight [343]. HSV-2 is inactivated by direct incubation with sulfated biopolymer as in vivo consequence of virucidal activity is related with amplification of antiviral activity [335].
6.6.3 ANTIOXIDANT ACTIVITY Free radicals are highly reactive molecules with an unpaired electron and are produced by radiation or as by-products of metabolic processes. They initiate chain reactions which lead to disintegration of cell membranes and cell compounds, including lipids, proteins, and nucleic acids [327]. Antioxidant compounds scavenge free radicals such as peroxides and reduce the level of oxidative stress and slow/prevent the development of complications associated with oxidative stresserelated diseases [344]. The use of algal biopolymers was totally ignored as an antioxidant agent but the recent studies revealed that algal compounds have considerable antioxidant competence [345]. As being photoautotrophs, micro/macroalgae possess a trenchant, antioxidant magpie complex for their self-defense against radical and oxidative stresses [346]. ROS (reactive oxygen species), i.e., superoxide anion, hydrogen peroxide, and hydroxyl radicals, dissimulate pharmaceutical security and diminish food quality by oxidation of lipids. Algal-sulfated biopolymers not only act as dietary fibers but also act as free-radical scavengers (Fig. 6.3), e.g., Tannin et al. [347] reported that Porphyridium spp. prevented autooxidation of linoleic acid and repressed oxidative damage to 3T3 cells caused by FeSO4. Their further studies revealed that the antioxidant activity was dose dependent having positive correlation with sulfur contents conferring free-radical scavenger activity. Carrageenans and
FIGURE 6.3 Antioxidant Activity of Algal Extract. : Inhibition by algal extract. A step at which algal extracts prevents the tissue damage by inhibiting lipid peroxidation, superoxide, peroxide, hydroxyl ions formation.
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ulvans bioactivities were found to be correlated with the contents of sulfate [348]. Fractions of fucan from Laminaria japonica and Fucus vesiculosus exhibited positive correlation between fucose and sulfate concentration to act as metal chelator and free-radical and insulin-dependent scavenger [349]. Sun et al. [350] reported that low molecular weight fractions (6.55 kDa) of sulfated biopolymers isolated from Porphyridium cruentum exhibited higher antioxidant activity against ascorbic acid than FeSO4-induced peroxides having high molecular weight (256 kDa) in mouse cells. Scientists reported that sulfated biopolymers of Arthrospira were stronger superoxide anion radical scavenger than a-tocopherol. Crude extract was two times stronger than a-tocopherol. Seaweeds also reported recognized antioxidants such as terpenoids [351], carotenoids, mycosporine-like amino acids, phlorotannins, ascorbic acid, tocopherols [352], and algal-sulfated polysaccharides [353]. Laminaria digitata and Himanthalia elongata have been reported to exhibit antioxidant activity comparable with those of vitamin E and butylhydroxyl toluene (BHT) [347]. Antioxidant activity was also reported from Sargassum micracanthum [354], Rhodomela confervoides, Symphocladia latiuscula [355], Kappaphycus alvarezzi [356,357], Gelidiella acerosa [358], F. vesiculosus [359], diphlorethohydroxycarmalol and 6,60 -bieckol isolated from Ishige okamurae [360], Undaria pinnatifida [361], ethanolic extract of Sargassum pallidum [362], Enteromorpha compressa, Capsosiphon fulvescens [363], Halimeda incrassate [364], Eisenia bicyclis, Kjellmaniella crassifolia, Alaria crassifolia, Sargassum horneri, and Cystoseira hakodatensis [365]. Fucoidan derivatives, oversulphated, acetylated, and benzoylated fucoidan isolated from L. japonica, show potential antioxidant activity in vitro [345,353]. In vitro antioxidant activity of iota, kappa, and lambda carrageenans, homofucan from the edible seaweed F. vesiculosus, and heterofucans from the seaweed Padina gymnospora were also reported [366]. Astaxanthin, an antioxidant obtained from Haematococcus pluvialis is marketed [348].
6.6.4 ANTICANCER ACTIVITY Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells. If the spread is not controlled (Fig. 6.4), it results in death. Isolation of cytotoxic antitumor substances from marine organisms was reported in several references during the last 40 years, while in recent years, hundreds of potential antitumor agents were isolated from marine origin especially from marine algae [367]. Biological properties of seaweeds such as reduction of plasma cholesterol, binding of biliary steroids, inhibition of carcinogenic fecal flora, binding of pollutants, stimulation of the immune system, and the protective effects of b-sitosterols seaweed suggested them as a potent therapeutic agent against breast cancer. The low rate of breast cancer in Japan is associated with high seaweeds consumption [368]. Certain algae have long been used in traditional Chinese herbal medicines for the treatment of cancer [369]. Sulfated polysaccharides, including fucoidans and carrageenans, inhibit tumor metastasis in rats by inhibiting the action of the tumor cellederived heparanases
6.6 Therapeutic Applications of Algae
FIGURE 6.4 Anticancer Mode of Action of Algal Extract. : Inhibition by algal extract. Algal polysaccharides inhibit the proliferation of various types of cancer and cell cycle arrest at G0/G1 S or G2/M phase. Apaf-1, apoptotic protease activator factor; Bax, Bcl-2-like protein; Bcl2, B-cell lymphoma2; P53, tumor protein.
involved in membrane crossing [370e372]. Carrageenan from Sargassum kjellmanianam [373] significantly inhibited S-180 and leukemia-1210 ascites tumor growth effect of mitomycin in mice [374]. Carrageenan from rodophyta was also found to stimulate lectin-dependent, cell-mediated cytotoxicity against HEp-2 human epipharynx carcinoma cells [375]. Various brown algae, namely Scytosiphon lomentaria, Lessonia nigrescens, L. japonica, Sargassum ringgoldianum, red algae, Porphyra yezoensis and Eucheuma gelatinae, and the green alga, Enteromorpha prolifera have shown antitumor activity against Meth-A fibrosarcoma [376]. Fucoidans isolated from brown seaweed Sargassum thunbergii have proven antitumor activity [377,378]. Ulvan extracted from Ulva lactuca has shown cytotoxicity against human colon cell line [29]. Facosterols isolated from Turbinaria conoides also displayed cytotoxicity against human (HU) cell lines [379]. Caulerpenyne isolated from Caulerpa taxifolia exhibited antitumor activity against HU neuroblastoma cell line by inhibiting microtubule assembly and tubulin aggregation [380]. Compounds of dihydroxysargaquinone and sargatriol from Sargassum tortile [381] and diterpene from Sargassum crispum are known for their cytotoxic activities [382].
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Cytotoxicity of fucodian extracted from Sargassum swartzii and Sargassum denticaprum against some human cancer cell lines [383], antitumor activity of Gracilaria corticata against Jurkat and molt-4 human cancer cell lines [384], Spyridia filamentosa against human prostate carcinoma epithelium-like cell lines DU-145 [385], S. swartzii, Cystoseira myrica, and Colpomenia sinuosa against Colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), tamoxifen-resistant breast ductal carcinoma (T47D-T.R), and estrogenindependent breast carcinoma (MDAMB468) cell lines [386], Arthrospira platensis, Dunaliella salina and Aphanizomenon flosaquae, and H. pluvialis against the growth of human leukemia cell line HL-60, and the biphenotypic B myelomonocytic leukemia cell line MV-4-11 [387] were reported.
6.6.5 ANTIINFLAMMATORY ACTIVITY Algal-sulfated biopolymers are potent immunomodulators with the ability to control the activity of immune cell activity and to stimulate the immune response [388]. Algal cell wall polysaccharides jolt an outcome and progression of disease by complex targets [24]. Intravenous injection of fucoidan reduced leukocyte rolling in meningitis and similarly also reduced leukocyte enlisting to peritoneum [389]. Commercially available (SigmaeAldrich Chemical Co.) fucoidan from F. vesiculosus exhibits antiinflammatory activity by inhibiting the cell adhesion process by binding with P- and L-selectins. Fucans from Fucus spp. C. okamuranus, Ascophyllum nodosum, and Laminaria spp. treat rats’ acute peritonitis by inhibiting leukocyte recruitment toward abdominal cavity [390]. In addition to impairment of selection actions, these sulfated biopolymers have the ability to completely inhibit elastase and heparanase responsible for degradation of membrane integrity (Fig. 6.5). It was reported that sulfated biopolymers had the ability to inhibit the complement activation by binding with C-4, anticipate schism product required for the synthesis of C-3 convertase [391]. Tissot and colleagues [392] succeeded to isolate low molecular weight fractions of fucoidan that have shown their ability to inhibit the complement by binding with immune complexes and also influence the C-1q and activate C-1 to recognize IgG. Structural elucidations using NMR revealed that branched fucoidan oligosaccharides are more potent than linear structures for inhibition of complement system [393,394]. Fucoidan influencing the complement system, also affect innate immunity rendering the pro-inflammatory state by reducing allergic reactions. Furthermore, it was also observed that sulfated algal cell wall polysaccharides also regulate innate immunity by binding with phagocytes and macrophages [395]. lcarrageenan generates cytokine response by stimulation of T-cell cultures in a TLR4 (toll-like receptor-4) in mice [396]. However, TLR4-deficient splenocyte mice also produced g-interferon after injection of l-carrageenan indicating that PRRs (proline-rich polypeptides), in addition to TLR4, were also provoked. It was reported that l-carrageenan might be applied to amend allergic reactions. U. pinnatifida fucoidan expressed similar results [397] in accordance with the
(A) Untreated inflammation; (B) treated inflammtion with sulfated polysaccharides [297].
6.6 Therapeutic Applications of Algae
FIGURE 6.5 Antiinflammatory Role of Sulfated Polysaccharides.
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findings of Tsuji et al. [396]. Reduction in inflammation is due to its interaction with other factors such as inducible nitric oxide synthase (iNOS) and cytokines, e.g., fucoidan isolated from F. vesiculosus incurred NO by attracting macrophages, causing the reduction in inflammation beyond impairment of LPS (lipopolysaccharide) [398]. Desulfation of sulfated polysaccharides from Ulva rigida is associated with complete attenuation of immunostimulatory activity [309]. Moreover, sulfated biopolymers from various species of algae, i.e., Phaeodactylum, Chlorella stigmatophora, and Porphyridium, were found to be effective antiinflammatory agents. Raposo et al. [399] reported that carrageenans and fucoidans aggravated the cytotoxicity of macrophages, lymphocytes, and natural-killer cells opposed to tumors. The antiinflammatory effect of Sagarssum hemiphyllum against Phorbol 12-myristate 13acetate (PMA) and A23187-induced interleukin-8 (IL-8) and on tumor necrosis factorea (TNF-a) secretion from human mast cells (HMC-1) [400], Galaxaura marginata against Croton oil induced mouse ear edema [401], S. thunbergii and Sargassum fulvellum against phorbol myristate acetate-induced ear edema, erythema, and blood flow [402], Porphyra dentata against LPS-induced RAW 264.7 macrophages [403], Petalonia binghamiae against ethyl acetate LPS-induced RAW 264.7 macrophages [404], S. swartzii and Ulva reticulata against Carrageenan-induce inflammation [405], Dichotomaria obtusata, against waterear edema induced by TPA and writhing-induced hind paw edema in rats and peritonitis for acute and chronic inflammatory mode by acetic acid [406], and T. conoides against carrageenan-induced hind paw edema [407] were also reported. On the basis of these reports, sulfated biopolymers can be used for therapeutic purposes in allergy and autoimmune diseases.
6.6.6 ANTIULCER ACTIVITY Chromene compound extracted from the seaweed S. micracanthum is reported to possess antiulcer property [408]. Methanolic extract of red algae Gracilaria changii shows antiulcer activity [409]. It is also exhibited by seaweeds Turbinaria ornata, Gracillaria crassa, and Laurencia papillosa [410].
6.6.7 ANTIDIABETIC ACTIVITY Diabetes is one of the most serious, chronic diseases that is developing with the increase in obesity and aging in the general population. It is largely classified into insulin-dependent diabetes mellitus (type-1 diabetes) and non-insulin-dependent diabetes mellitus (type-2 diabetes) [411e413]. Phlorotannins derived from brown algae exhibited their various antidiabetic mechanisms such as a-glucosidase and a-amylase inhibitory effects (Fig. 6.6). Dieckol, Fucodiphloroethol G, 6,60 -Bieckol, 7-Phloroeckol, Phlorofucofuroeckol-A isolated from Ecklonia cava; Phloroglucinol, Eckol, and Dioxinodehydroeckol isolated from Ecklonia Stolonifera and Ecklonia bicyclis; and Octaphlorethol-A isolated from Ishige foliacea show antidiabetic
6.6 Therapeutic Applications of Algae
FIGURE 6.6 Schematic Presentation of Antioxidant Activity of Algal Extracts. : Inhibition by algal extract. Algal extracts prevents from diabetic complications by inhibiting the production of sorbitol, free radicals, and oxidative stress expressed by cross sign.
effects [395]. Octaphlorethol-A (OPA), a type of phlorotannin isolated from Ishige foliacea, is shown to have antidiabetic activities [414]. Diphlorethohydroxycarmalol (DPHC) isolated from I. okamurae is a potent inhibitor for a-glucosidase and a-amylase [415]. Seaweed lipids also show antidiabetic activity [416].
6.6.8 ANTITHROMBIN ACTIVITY Strong antithrombin or antithrombotic activity is exhibited by fucoidans isolated from Laminaria saccharina, L. digitata, Fucus serratus, Fucus distichus, and Fucus evanescens [390]. A novel sulfated galactofucan isolated from Spatoglossum schroederi showed potent antithrombotic activity [417]. A fucan sulfate isolated from E. kurome [418] and S. schroederi exhibited antithrombic activity [419]. A bromophenol derivative named (þ)-3-(2,3-dibromo-4,5-dihydroxy-phenyl)-4-bromo-5,6dihydroxy-1,3-dihydroiso-benzofuran, isolated from brown alga Leathesia nana, also exhibited good in vivo antithrombotic activity [420].
6.6.9 ANTIOBESITY ACTIVITY Obesity is a medical condition of excess body fat accumulation that impairs health. It is a major health problem throughout the world and an issue of growing concern in the 21st century. According to the World Health Organization, overweight and
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obesity are the fifth leading risk for global death, and at least 2.8 million adults die each year as a result of being overweight or obese. It is associated with the development of metabolic diseases such as type-2 diabetes as well as cardiovascular disorders, some types of cancer, and osteoarthritis [421]. Obesity is controlled by controlling appetite, blocking fat absorption, stimulating energy expenditure, suppressing adipose tissue growth, and by increasing body fat mobilization. Algal polysaccharides chitin and chitosan isolated from green algae, and alginate and fucoidan from brown algae show potential for weight loss with different mechanisms. Antiobesity effect of phlorotannins 7-phloroeckol, fucofuroeckol-A and eckol isolated from Ei. bicyclis and E. cava; carotenoids fucoxanthin from Ei. bicyclis and U. pinnatifida; astaxanthin isolated from H. pluvialis have also been reported [422]. Green algae carotenoid siphonaxanthin shows potent antifat activity [423].
6.6.10 ANTIANGIOGENIC ACTIVITY Angiogenesis results in new blood vessel formation from a preexisting vasculature that occurs under either physiological or pathological conditions [424]. In pathological conditions, such as inflammatory diseases, rheumatoid arthritis, and tumor metastasis, a chronic, unregulated angiogenic state often helps spreading of the diseases (Fig. 6.7). Hence preventing angiogenesis under pathological conditions is a promising approach in the prevention of cancer and other angiogenic-related diseases [425]. Algal carotenoid fucoxanthin effectively suppressed the differentiation of endothelial progenitor cells into endothelial cells involving new blood vessel formation (Fig. 6.7). Fucoxanthin and fucoxanthinol suppressed microvessel outgrowth in vivo and ex vivo angiogenesis assay using a rat aortic ring [426]. Antiangiogenic effect is also exhibited by siphonaxanthin derived from green algae Codium fragile [427].
6.6.11 HEPATOPROTECTIVE ACTIVITY Phloroglucinol and phloroglucinol derivatives eckstolonol, phlorofucofuroeckol-A (Fig. 6.8) isolated from the brown alga Ecklonia stolonifera exhibit hepatoprotective activity [428]. Hepatoprotective activities of carotenoids, b-carotene, and xanthophyll from microalgae, Spirulina platensis, and D. salina [429], and low molecular weight sulfated polysaccharide isolated from L. japonica were also reported [430]. Phloroglucinol protects liver damage due to oxidative stress produced by tributyl hydroperoxide (T-BHP), carbon tetra chloride, etc.
6.6.12 RADIOPROTECTIVE EFFECT Ionizing radiations are known to generate reactive oxygen species in irradiated tissue and cells. The primary damage caused by radiation is production of aqueous free radicals, generated by the action of radiation on water within the cell. These free radicals react with cellular macromolecules such as DNA, protein, and lipid membrane
6.6 Therapeutic Applications of Algae
FIGURE 6.7 Antiangiogenic Effect of Algal Derived Fucoxanthin. : Inhibition by algal extract. Algal extracts inhibits the synthesis of tumor by inhibiting the VEGF. EGF, epidermal growth factor; PDGF, platelet derived growth factor; VEGF, vascular endothelial growth factor.
causing cell dysfunction and mortality. Lungs are reported to be especially sensitive to oxidative stress. Eckol, a trimeric phloroglucinol with a dibenzeno-1,4-dioxin skeleton, one of the major phlorotannins isolated from brown alga E. cava is found to be a radioprorective agent. It acts by reducing the intracellular reactive oxygen species generated by g-ray radiation (Fig. 6.9). Moreover, eckol also protected against radiation-induced cellular DNA damage and membrane lipid peroxidation [431].
6.6.13 ANTI-ALZHEIMER ACTIVITY Alzheimer’s disease (AD) is an irreversible, progressive, neurodegenerative disorder of the central nervous system associated with progressive cognitive memory loss [432]. Neuropathological studies demonstrated that AD was associated with deficiency of the brain neurotransmitter acetylcholine (ACh). The inhibition of
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CHAPTER 6 Algae-Based Biologically Active Compounds
FIGURE 6.8 Hepatoprotective Effect of Algal Polymers. Phloroglucinol protects liver damage due to oxidative stress produced due to tributyl hydroperoxide (T-BHP), carbon tetra chloride, etc.
acetylcholinesterase (AChE) enzyme, which catalyzes the breakdown of ACh, can be one of the most realistic approaches to the symptomatic treatment of AD [433]. Methanolic extracts of marine algae Caulerpa racemosa, Codium capitatum, Ulva fasciata, Halimeda cuneata, Amphiora ephedraea, Amphiora bowerbankii, Dictyota humifusa [434], Hypnea valentiae, P. gymnospora, Ulva reticulate, and
FIGURE 6.9 Radioprotective Mode of Action of Phlorotannin. Phlorotannin from Ecklonia cava protects from radiation by activating immune system through increasing the levels of glutathione, oxidative enzymes, and free-radical scavengers whereas lowers apoptosis, mutation, and free-radical production.
6.6 Therapeutic Applications of Algae
Gracilaria edulis exhibit acetylcholinesterase inhibitory activity [435]. Fucosterol and 24-hydroperoxy 24-vinylcholestrol was isolated from n-hexane fraction of frozen Hypomecis formosana. Eckstolonol, eckol, phlorofucofluoroeckol0003A, dieckol, 2-phloroeckol, and 7-phloroeckol were isolated from the EtOAc extracts of Ecklonia stolonifera [436]. MeOH extracts and EtOAc extracts of I. okamurae exhibit inhibitory potential against AChE. 6,60 -bieckol isolated from I. okamurae serve as a potential AChE inhibitor that could be used as a potential functional food ingredient or nutraceuticals for preventing Alzheimer’s disease [437]. Sargaquinoic acid isolated from Sargassum sagamianum [438] and a glycoprotein from U. pinnatifida UPGP also exhibit acetylcholinesterase (AChE) inhibitory activity [439].
6.6.14 ACE INHIBITION ACTIVITY Increased blood pressure or hypertension is one of the major chronic medical condition, and one of the major independent risk factors for cardiovascular diseases. Angiotensin-I converting enzyme (ACE) plays a significant physiological role in regulating blood pressure by converting angiotensin-I to angiotensin-II, a potent vasoconstrictor. Therefore the inhibition of ACE activity is a major target in the prevention of hypertension (Fig. 6.10). The ethanol extract of E. cava, Ecklonia stolonifera, Phlorotannins such as eckol, phlorofucofuroeckol-A, and dieckol derived from E. stolonifera have shown considerable inhibitory activity against ACE [440]. Aqueous extracts of red algae Lomentaria catenata and Lithophyllum okamurae, methanolic extracts of Ahnfeltiopsis flabelliformis show inhibitory activity against ACE [441].
6.6.15 ANTITUBERCULOSIS ACTIVITY Antituberculosis activities of red algae Gelidium sp. were studied. Ether and alcoholic extracts of Gelidium amansii have shown a slight inhibition against M. tuberculosis while acetone extract of Gypsophila capillaris exhibited considerable inhibition toward Mycobacterium avium and Mycobacterium tuberculosis [442]. Diterpene, (1E,2R,3R,4S,6E,18S)-4,18-dihydroxydictyolactone isolated from the methanol extract of the brown alga Dictyota sp. exhibit weak antituberculosis activity [443]. Caulerpin a bis-indole alkaloid isolated from C. racemosa and Caulerpa serrulata exhibit excellent activity against M. tuberculosis. Biological results indicated that Caulerpin may be useful as a lead compound for the development of novel antituberculosis agents [444].
6.6.16 INSECTICIDAL ACTIVITY Polyhalogenated monoterpenes isolated from the red alga Plocamium cartilagineum exhibit insecticidal activity against the aster leafhopper [445]. Telfairine a monoterpene isolated from the red alga Plocamium telfairia shows strong insecticidal activity
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CHAPTER 6 Algae-Based Biologically Active Compounds
FIGURE 6.10 ACE (Angiotensin Converting Enzyme) Inhibition Role of Algal Extract. : Inhibition by algal extract. Algal extract acts on angiotensin converting enzyme. Algal extract inhibits the enzyme responsible (ACE and angiotensin-II) for hypertension and heart failure.
against the mosquito larvae Culex pipiens pallens [140]. Isodomic acids isolated from the red alga Chondria arnata show significant insecticidal activity when they are injected subcutaneously into the abdomen of American cockroach [446].
6.6.17 HYALURONIDASE-INHIBITION ACTIVITY Hyaluronidase is an enzyme that depolymerizes the polysaccharide hyaluronic acid in the extracellular matrix of connective tissue. The enzyme is known to be involved in allergic effects and migration of cancer and inflammation. Phlorotannins, phloroglucinol, such as eckol, phlorofucofuroeckol-A, dieckol, and 8,8-bieckol isolated from the brown algae Ei. bicyclis and E. kurome were reported to exhibit a stronger inhibition effect against hyaluronidase compared to well-known inhibitors such as catechin and sodium cromoglycate [447].
6.6 Therapeutic Applications of Algae
6.6.18 ANTIFUNGAL ACTIVITY A meroterpenoid isolated from the brown alga Cystoseira tamariscifolia, characterized as methoxybifurcarenone, possesses antifungal activity against three tomato pathogenic fungi [142]. Hexane extracts of three algal species Dictyota dichotoma, D. dichotoma var. implexa, and Dilophus spiralis exhibited a wide spectrum of antifungal activities having ability from process of cell membrane permeability to metabolic disruption (Fig. 6.11) which varied during the seasons [448]. Terpenoids isolated from algal species Stypopodium zonale, Laurencia dendroidea, A. nodosum, Sargassum muticum, Pelvetia canaliculata, Fucus spiralis, Sargassum filipendula, Sargassum stenophyllum, Laminaria hyperborea and G. edulis. S. zonale, L. dendroidea, P. canaliculata, S. muticum, A. nodosum, and F. spiralis possess antifungal activity; their extracts significantly inhibited the Colletotrichum lagenarium growth [449].
6.6.19 ANTIMALARIAL ACTIVITY Snyderol sesquiterpene derivative isolated from the red alga Laurencia obtusa was active against D6 and W2 clones of the malarial parasite Plasmodium falciparum [450]. Sphaerococcenol-A isolated from red alga Sphaerococcus coronpifolius is responsible for the antimalarial activity of the extract, against the chloroquineresistant P. falsciparum FCBI strains with an IC50 of 1 mM [451].
FIGURE 6.11 Antifungal Mode of Action of Algal Extract. : Inhibition by algal extract. Different steps at which algal extracts inhibit the synthesis of ergosterol, microtubules and DNA replication.
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6.6.20 ANTIGLYCEMIC AND ANTILIPIDEMIC EFFECTS It was reported that macroalgal cell wall polysaccharides had an ability to decrease TG (triglycerides) and cholesterol [27], but unfortunately this area of research for microalgae is not appropriately investigated. In spite Ginzberg and colleagues [452] reported that modified fatty acid profile improved carotene contents in chicken egg yolks after the injection of Porphyridium sulfated biopolymer. Furthermore, considerably low levels of insulin and glucose, VLDL, and serum cholesterol, and improved levels of hepatic cholesterol without any toxic effect were observed when polysaccharides of both Porphyridium and R. reticulate were used in combination in rats [453,454]. Huang et al. [242] suggested that sulfated polysaccharides of Porphyridium as potent antilipidemic (Fig. 6.12) and antiglycemic agent have the ability to reduce blood-glucose levels without any modification of islets of Langerhans. Due to rich contents of fibers, algal polysaccharides acts as bile acids binder, cation exchangers, and hypocholesterolemic agent could be used as nutraceuticals [455]. Algal-sulfated polysaccharides affect the absorption of nutrients, lower the lipid absorption and micelles formation, and make internal contents more viscous, and are therefore known as potent fibers [456]. They are equally effective in coronary heart disease by increasing bile excretion [457]. Fucans isolated from Sargassum polycystum were reported to have a significant antilipidemic effect in
FIGURE 6.12 Antilipidemic Mode of Action of Algal Sulfated Polysaccharides. : Inhibition by algal extract. Algal extract inhibits the synthesis of cholesterol via HMG 3hydroxy-3-methylglutaryl-CoA (HMG), isopentenylpyrophosphate squalene synthesis.
6.6 Therapeutic Applications of Algae
liver tissues and serum in hepatitis caused by acetaminophen toxicity [458]. Sulfated Sargassum wightii polysaccharide caused the normalization of lecithinecholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL) of plasma in nephrotoxicity [459]. Sulfated polysaccharides acted as potent renoprotective agent by reducing the LDL oxidation. Fucoidan from L. japonica were suggested as antilipidemic, showed their potency by raising LPL, HL (hepatic lipase), and LCAT, thus rendering LDL and TG levels while elevating HDL levels. Sulfated polysaccharides from F. vesiculosus affected the serum cholesterol and TG levels in dose-subsidiary-tone, e.g., smaller fractions of Ulva pertusa did not reduce the serum cholesterol, but only caused the normalization of TG by raising HDL [460]. It was observed that many sulfated biopolymers, by attracting the enzymes present on heparin-binding sites, influenced HL and LPL, e.g., fucoidan isolated from F. vesiculosus stabilized LPL activity by binding with heparin-binding sites [27]. Drug-toxicities-associated hyperlipidemia is effectively addressed by algal cell wall polysaccharides. Fucoidan polysaccharide sulfuric acid ester from L. japonica reduced the concentration of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL) of hyperlipidemic rats, and increased the concentration of high-density lipoprotein cholesterol (HDL). The treatment also increases the activities of lipoprotein lipase (LPL), hepatic lipoprotein (HL), and LCAT in serum [461]. Antilipidemic effect is also reported from the ulvan polysaccharide of U. pertusa [462].
6.6.21 ANTIALLERGY ACTIVITY Allergic diseases are one of the major public health problems in the developed world. It was estimated that approximately one-third of the general population was affected by allergic diseases. These diseases include asthma, dermatitis, beesting allergy, food allergy, conjunctivitis, and severe systemic anaphylaxis [463]. A large number of antiallergic agents from marine algae were identified. Several bioactive phloroglucinol derivatives, fucodiphloroethol G, eckol, dieckol, 6,6bieckol, phlorofucofuroeckol-A, and 1-(30 ,50 -dihydroxyphenoxy)-7-(200 ,400 ,6trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin isolated from E. cava are evidenced to be efficient against A23187 or Fc RI-mediated histamine release from KU812 and RBL-2H3 cells [464,465]. The red algae Carpopeltis affinis was confirmed to be effective against atopic allergic reactions in vitro [466]. The ethanolic extracts of edible red alga Laurencia undulata and brown alga E. cava exhibit a significant inhibition of all asthmatic reactions in OVA-induced mice [467,468]. Alginic acid, a naturally occurring hydrophilic colloidal polysaccharide obtained from several species of brown seaweeds, exhibits inhibitory effects against hyaluronidase activity and histamine release from mast cells [469]. Phycocyanin, one of the major pigment constituents of blue-green microalgae Spirulina, has been found to be an inhibitor of different allergic responses such as histamine release from rat peritoneal mast cells (Fig. 6.13), ear swelling in mice induced by OVA, and skin reactions in rats caused by histamine [470].
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FIGURE 6.13 Antiallergy Mode of Action of Algal Extract. : Inhibition by algal extract. Algal extract protects from allergic reactions by inhibiting the synthesis of prostaglandin E2.
6.6.22 ANTIFEEDENT ACTIVITY Antifeedent activity of two diterpenoids with a novel skeleton, dictyterepenoids A and B isolated from the brown algae Dilophus okamurae was reported against young abalone [471]. Crude organic extract of brown alga Dictyota pfaffii significantly exhibits antifeedent activity against sea urchin Lytechinus variegatus and generalist herbivore fishes [472].
6.6.23 ANTIADHESIVE EFFECT Algal cell wall polysaccharides are potent antiadhesive agents as they inhibited the pathogenic adhesion. Currently, several algal polysaccharides were isolated which affect the adherence of fish pathogens to skin, gills, and gut, and Helicobacter pylori to HeLa S3 [473]. Consequential impersonation of carbohydrate moieties of sulfated polysaccharides in provision of recognition sites for infection attachment was already been reported, e.g., heparin sulfates [474]. Antiadhesive property of heparin sulfate is contributed due to its molecular stereochemistry and net charge [475]. However, due to certain risk associated with use of sulfated polysaccharides as antiadhesive agent, further studies to understand cytotoxicity are needed.
6.6.24 BIOLUBRICATING AGENT Very little is known about the use of sulfated polysaccharides as biolubricants. However, Arad et al. [476] first time reported the lubricating properties of Porphyridium exopolysaccharides ascribable to its rheological idiosyncrasy [477]. Arad and coworkers suggested sulfated polysaccharides as better lubricating agent for joints than ordinary lubricating agents, i.e., hyaluronic acid, hydrogel, as they were thermostable [477]. In
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addition to these, they also reported that incubation of sulfated polysaccharide of Porphyridium with hyaluronidase did not show any significant change in viscosity while only 1% polysaccharide exhibited significant lubricating properties under high load. They concluded from their experiments that hyaluronic acid could be locum with sulfated biopolymers and could be used in the manufacturing of joint-lubricating solutions to alleviate the severity of arthritis.
6.6.25 DRAG-REDUCING AGENTS Very little is known for algal-sulfated polysaccharides as drag-reducing agents. Exclusively a couple of studies were made to check the drag-reducing potential of sulfated polysaccharides to extend their functional characteristics for engineering purposes. Gasljevic et al. reported that exopolysaccharides of microalgae have potential to act as drag reducers. Exopolysaccharides of both R. maculate and P. cruentum were found to be very potent drag reducers in very low concentration followed by Schizochlamydella [478].
6.6.26 OTHER APPLICATIONS It was reported that both micro- and macroalgae had their potential in nutraceuticals, functional foods, and health food industry [457]. Yet, due to their rheological characteristics and chemical composition, they also have diverse applications in other fields, e.g., cosmetics, prophylactic therapy. In conclusion to all applications of algal cell wall polysaccharides, adhesion is seemed to be more important as it is not only involved in algal movement but also in sand and soil particle aggregation, affecting cohesiveness and stability of sediments [479].
6.7 CONCLUSION This chapter briefly described algal classification and their possible pharmacological and therapeutic applications with respect to phytochemical constituents. This is an attempt to compile and document comprehensive information on different aspects of algae to help scientific community for further research and investigative study.
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<p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>1</p><p>ContentsINDIAN HISTORY GEOGRAPHY- PHYSICAL AND ECONOMIC THE SCIENCES INDIAN POLITY THE POTPOURRI INDIAN HISTORY ANCIENT INDIAo o o o o o o o o o o o o o o o THE HARAPPAN CULTURE THE RIGVEDIC CIVILZATION THE LATER VEDIC TIMES JAINISM BUDDHISM THE FIRST MAGADHAN EMPIRE IRANIAN AND MACEDONIAN INVASIONS THE INDO-GREEKS THE SATVAHANAS THE GUPTAS HARSHA AND HIS TIMES SCIENTIFIC LEGACY OF ANCIENT INDIA MAJOR PHILOSOPHICAL SYSTEMS IN ANCIENT INDIA MAJOR TERMS USED IN ANCIENT LITERATURE SOME MAJOR ANCIENT CLASSICS MAJOR MONUMENTS</p><p>MEDIEVAL INDIAo o o o o o o o o o o o o o THE CHOLA EMPIRE THE CIRCA 1000-1200 AD THE DELHI SULTANATE- I THE CIRCA 1200-1400 AD THE DELHI SULTANATE- II THE CIRCA 1200-1400 AD VIJAYANAGARA KINGDOM AND THE PORTUGUESE CIRCA-1350-1365 THE SUFI AND THE BHAKTI MOVEMENTS THE MUGHALS AND THE AFGHANS THE GREAT MUGHALS CLIMAX AND DISINTEGRATION OF THE MUGHAL EMPIRE-I IMPORTANT CLASSICS WRITTEN DURING MEDIEVAL TIMES SOME FAMOUS BHAKTI POETS IMPORTANT TERMS AND MEANINGS THEREOF IMPORTANT FOREIGN VISITORS IMPORTANT TITLES AND HOLDERS THEREOF</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>2</p><p>MODERN INDIAo o o o o o o o o o o o o o o o o o o o o o o THE EAST INDIA COMPANY -1600-1714 THE PERIOD-1765-1856 THE REVOLT OF 1857 THE POST-1857 SCENARIO THE ROLE OF THE PRESS THE WORK IN LEGISLATIVE COUNCILS THE SWADESHI MOVEMENT THE CONGRESS SPLIT AND THE REVOLUTIONARY TEERORISTS-I THE GHADAR THE HOME RULE MOVEMENTS GANDHIJIS ACTIVISM THE EARLY PHASE THE NON-COOPERATION MOVEMENT -1920-22 THE REVOLUTIONARY TERRORISTS-II THE CIVIL DISOBEDIENCE MOVEMENT THE YEARS AFTER THE CRIPPS MISSION SOCIAL REFORM AND OTHER ORGANIZATIONS GOVERNOR-GENERALS AND STEPS/ INITIATIVES REGIONAL & TRIBAL UPRISINGS AND LOCATIONS IMPORTANT TITLES AND HOLDERS THEREOF IMPORTANT PRESIDENTS BOOK/NEWSPAPER/JOURNAL- AUTHOR/EDITOR MISCELLANEOUS</p><p>GEOGRAPHY- PHYSICAL AND ECONOMICo o o o o o o o o o o o o o o ASTRONOMICAL TERMS SOME GEOGRAPHICAL FACTS GEOGRAPHICAL TERMS THE MINERAL WEALTH OF INDIA MAJOR TOURIST MONUMENTS IN INDIA MAJOR INDUSTRIAL CENTRES IN INDIA MAJOR CITIES ON RIVER BANKS (INDIA) CHANGED NAMES OF SOME CITIES/ COUNTRIES CONTINENTS, POPULATIONWISE MAJOR PORTS IN INDIA MAJOR CITIES ON RIVER BANKS (WORLD) DEMOGRAPHIC FACTOIDS (1991 CENSUS) MISCELLENEOUS DEMOGRAPHIC FACTFILE COMPARATIVE LITERACY LEVELS ACROSS INDIA GEOGRAPHICAL EPITHETS</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>3</p><p>PHYSICAL GEOGRAPHYo o o o o o o o o o o o o o o o o o o o o o o o o o o THE EARTH ROCK TYPES HYDROLOGICAL CYCLE WATER MOVEMENTS THE BIOSPHERE FACES OF THE LAND WEATHERING DEGRADATION AND AGGRADATION RIVERS GLACIERS WINDS WAVES PLATE TECTONICS VOLCANOES EARTHQUAKES TEMPEARTURE ZONES LATITUDINAL ZONES TEMPERATE ZONES LAND AND SEA CONTRASTS PREVAILING WINDS OCEAN CURRENTS DIURNAL AND SEASONAL CYCLES PRESSURE AND WINDS SEASONAL MIGRATION LAND AND SEA BREEZES PRECIPITATION FOREST TYPES</p><p>THE SCIENCES THE PHYSICAL WORLDo o o o o o o o o o o o o o MATTER SOLID LIQUID GAS CHARLESS LAW MASS WEIGHT MASS AND WEIGHT DENSITY SPECIFIC GRAVITY STREAMLINING MOTION SPEED UNIFORM SPEED</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>4</p><p>o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o</p><p>ACCELERATION RETARDATION OR DECELERATION NEWTONS FIRST LAW OF MOTION NEWTONS SECOND LAW OF MOTION NEWTONS THIRD LAW OF MOTION GRAVITY LAW OF GRAVITATION RELATIVE VELOCITY ERG POWER ENERGY EQUILIBRIUM SURFCAE TENISON VISCOSITY PASCALS LAW ARCHIMEDES PRINCIPLE PRESSURE HEAT TEMPERATURE CALORIE LATENT HEAT EVAPORATION TRANSFERENCE OF HEAT LATENT HEAT OF VAPORISATION LATENT HEAT OF FUSION RECTILINEAR PROPAGATION OF LIGHT REFLECTION REFRACTION MAGNETISM CURRENT ELECTRICITY HEATING EFFECTS OF CURRENT LIGHTING EFFECTS MAGNETIC EFFECTS MICROWAVES MICROWAVE COOKER ATOM BOMB PULSARS QUARTZ CLOCK RADAR REFRIGERATOR ROCKET SOLAR COOKER TELESCOPE SOUND</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>5</p><p>CHEMICAL PHENOMENAo o o o o o o o o o o o o o o o o o o o o o o o PHYSICAL CHANGE CHEMICAL CHANGE ELEMENT COMPOUND MIXTURE HARD AND SOFT WATER ALLOY AMALGAM CHEMICAL NAMES IMPORTANT LAWS IN SCIENCE AND SOME DEFINITIONS PRINCIPLES OF SCIENTIFIC INSTRUMENTS ATOMIC POWER PLANT NUCLEAR FUSION CINEMA DYANMO JET ENGINE KALEIDOSCOPE MEDICAL IMAGING NUCLEAR MAGNETIC RESONANCE RADIOACTIVITY LIGHT YEAR PHOTO-ELECTRIC EFFECT MISSILES</p><p>THE BIOLOGICAL WORLDo o o o o o o o o o o o o o o o o o ANIMAL AND PLANT GROUPS STRUCTURAL ORGANIZATION MITOSIS MEIOSIS TWINS CLONING GENE EXPRESSION AND GENETIC DSIORDERS HEREDITY SEX-LINKED GENES AND RELATED DISORDERS THEORIES OF BIOLOGICAL EVOLUTION INFECTIOUS DISEASES VACCINATION NUTRITIONAL DEFICIENCY DISORDERS FOOD AND NUTRITION BLOOD GROUPS GLANDS SENSE ORGANS SCIENTIFIC UNITS OF MEASUREMENT</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>6</p><p>INDIAN POLITYo o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o THE PREAMBLE INTRODUCTION TO THE INDIAN CONSTITUTION SOURCES OF INDIAN CONSTITUTION POINTS TO REMEMBER THE FEDERAL SYSTEM TERRITORY OF THE UNION ACT/LEGISLATION FUNDAMENTAL RIGHTS FUNDAMENTAL DUTIES DIRECTIVE PRINCIPLES OF STATE POLICY PROCEDURE FOR AMENDMENT THE BASIC FEATURES THEORY THE UNION EXECUTIVE THE UNION COUNCIL OF MINISTERS THE ATTORNEY GENERAL OF INDIA THE COMPTROLLER AND AUDITOR GENERAL OF INDIA THE UNION LEGISLATURE LEGISLATIVE PROCEDURES PUBLIC ACCOUNTS COMMITTEE THE STATE EXECUTIVE SPECIAL STATUS OF J&K THE INDIAN JUDICIAL SYSTEM THE FINANCE COMMISSION THE UNION AND STATE PUBLIC SERVICE COMMISSIONS ELECTIONS IN INDIA THE SCHEDULED CASTES AND SCHEDULED TRIBES OFFICIAL LANGUAGES IMPORTANT SCHEDULES SOME MAJOR CONSTITUTIONAL AMENDMENTS MISCELLANY INDIAN PRESIDENTS SO FAR INDIAN PRIME MINISTERS SO FAR SOME IMPORTANT POLITICAL TERMS</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>7</p><p>THE POTPOURRIo o o o o o o o o o o o o o o o o o o o o o MISCELLANEOUS TERMS HISTORICAL, POLITICAL, CONSTITUTIONAL AND DIPLOMATIC TERMS LEGAL TERMS LITERARY, ARTISTIC AND JOURNALISTIC TERMS MEDICAL TERMS SCIENTIFIC TERMS AND INSTRUMENTS DIFFERENT AREAS OF KNOWLEDGE MAJOR INSTRUMENTS SOME INTERNATIONAL BOUNDARY LINES OTHER SPECIALIZED INTERNATIONAL AGENCIES NON-GOVERNMENTAL ORGANIZATIONS NATIONAL AWARDS AND HONOURS GALLANTRY AWARDS OTHER NATIONAL AWARDS INTERNATIONAL AWARDS AND HONOURS BOOK N AUTHORS FIRST IN THE WORLD FIRST IN INDIA DANCE, MUSIC, CULTURE . COMPOSERS/ MUSICIANS INSTRUMENTALISTS VOCALISTS</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>8</p><p>INDIAN HISTORYANCIENT INDIA* The Earth is nearly 4000 million years old as supported by scientific evidence and the evolution of its crust shows four stages. The fourth stage is called the Quaternary, which is divided into Pleistocene (most recent) and the Holocene (the present); the former lasted between 1, 000,000 and 10000 years before the present and the latter began about 10000 years ago. * Man appeared on the Earth in Africa about 2.6 million years ago. * 1. The Paleolithic Age: The stone-age whose characteristic features were the use of hand-axes, cleavers and choppers, flakes, blades etc. The rock-shelters and caves at Bhimbetka near Bhopal can be cited as major evidences pointing towards it. In the world context, the upper or the last Paleolithic age marks the appearance of the modern man (Homo sapiens) on earth. * 2. The Mesolithic Age: The Mesolithic Period is a transitional phase between the Paleolithic and the Neolithic ages. It is marked by warmer climates, hunting, fishing and food gathering and domestication of animals. The peculiar tool of the people was the microlith, evidence of which can be found in Bogor in Rajasthan. * 3. The Neolithic Age: In the world context, the New Stone Age began around 9000 BC. The people of these times used tools made of polished stone. The domestication of animals became a major economic activity. The only neolithic settlement in India is found in Mehergarh in Rajasthan. * The Chalcolithic Cultures: The end of the neolithic phase saw the use of metals, of which copper was the first to be used. Several cultures were based on the use of stone and copper implements. Such a culture is referred to as a Chalcolithic culture, referring to the use of both copper and stone. Technologically, this represents the pre-Harappan phase because the Harappan civilization was based on the use of bronze. They domesticated animals, practiced agriculture (wheat, rice and bajra).*********************************************************************************************************</p><p>THE HARAPPAN CULTURE : THE BRONZE AGE* The Harappan Civilization flourished on the banks of the river Indus. It was discovered first of all in Harappa in Pakistan by DR Sawhney and RD Banerjee in 1921. * Another prominent excavated site is the Mohanjo-daro (which literally means the mound of the dead people) in Sindh. * Some other places containing the remains of this civilization include Kalibangan (Rajasthan), Dholavira and Lothal (Gujarat), Banawali (Hissar), Chanhu Daro (Sindh) and Sanghol (Panjab). * The most distinguishing feature is the town-planning system and architecture. Burnt bricks find use on a wide scale for the first time here. The towns are built on scientific lines, with roads cutting each other at right angles and having covered drains. * Two sites stand out --- The Great Bath and the Great Granary of Mohenjo-daro. The Great Granary is the largest building in Mohanjo-daro. * Rice has been found in Lothal (Gujarat), which was used as a port also. The Indus people were the first to produce cotton; that is why the Greeks refer to it as Sindon (derived from Sindh).</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>9</p><p>* Mercantile activities were most important in those times. Numerous seals, weights and measures attest to it. The Harappans carried on international business in the Persian Gulf region and long-distance trade in lapis lazuli, a precious stone. * The Mother Goddess was a major object of worship. The worship of the Pashupati Maharaj (who later came to be known as Shiva) was also quite prevalent. Of animals and trees, they used to worship the bull and the pipal the most. * We find many seals and figurines made of terracotta. We also find a metal image of a dancing girl. They represent the biggest artistic achievements of these people. * It existed between 2500 BC and 1800 BC.*********************************************************************************************************</p><p>THE RIGVEDIC CIVILIZATION* We come to know of Aryans from the Rig Veda, which is the earliest specimen of the Indo-European languages. It is a collection of prayers devoted to different gods. * The Rig Veda has ten chapters, which give us valuable information about these people. * The Aryan civilization flourished on the river Sindhu. The Aryans appeared in India a little later than 1500 BC. and the use of horses played a significant role in their conquest of West Asia. * The Aryans always led a nomadic life. Their major occupation was pastoral (animal-rearing) in nature and cow was the chief animal they domesticated. So many references to cow are found in the Rigveda that it seems their entire life revolved around it. Mostly the Aryans fought for the sake of cows. A war is referred to as gavishti in vedic literature, which means a search for cows. * We find two very important political assemblies: The Sabha and The Samiti. We find evidence of election of the king (rajan) by the samiti. The samitis were very powerful. The two priests who played a very significant role in these times are Vashishta and Vishwamitra. The tribal chiefs got voluntary offerings from the people called bali. * The king did not maintain a standing army and used to muster a militia in times of need. A fighting unit was called a grama and its chief as gramini. * The Rig Vedic society was an egalitarian one, with no sharp discrimination against any particular class or section of people. Women were held in high esteem and could participate in political assemblies. * They worshipped different manifestatosn of nature. For instance, their chief god was Indra (The Rain God), Agni (The Fire God), Varuna (The Protector of the Universe), Usha (The God of The Morning Sun), Marut (The Wind God) and Soma (The God of Plants).*********************************************************************************************************</p><p>THE LATER VEDIC TIMES (1000 BC 600 BC)* For singing the Rig Vedic hymns were set to tune, and this collection of musical hymns came to be known as the Sama Veda. Besides, the later Vedic period also saw the compilation of the Yajur Veda (containing rituals and ceremonies) and the Atharva Veda (containing charms and spells). * Iron was used in plenty, which is referred to as shyama or Krishna ayas. Rice (vrihi) and wheat became their chief crops. Copper was used in abundance in making ornaments, implements etc. Agriculture became a primary livelihood and the peasants produced enough to maintain themselves as well as spare something for taxes.</p><p>Bulls Eyewww.hitbullseye.com</p><p>Learning Curve GK Theory</p><p>10</p><p>* Popular assemblies lost their importance and royal power increased at their cost. The sabha and samiti did continue, but their character changed a lot. Womens status declined to some extent. * The society became sharply divided into four varnas called the brahamins (the teachers and preachers), kshatriyas or rajnyas (warriors and rulers), vaishyas (the farming and mercantile class) and the shudras (menial servants). Since rituals were a central feature of this age, the brahmins gained a lot of social prestige and dominance. * The major tax-paying class was the vaishyas, mainly engaged in farming, business and artisanship. The kshatriyas generally became warriors and rulers. The shudras were generally farmhands and domestic servants. * Prajapati (The Creator) came to be worshipped as the supreme god. Some other later Vedic gods include Rudra (The God of Animals) and Vishnu who was thought to be the preserver and protector of the universe. * Sacrifices became central to worship, which were accompanied by ritualistic formulae to be pronounced carefully. * The later Vedic period also saw the formation of territorial kingdoms and the famous Mahabharta War is attributed to this period. However, a state system was not yet in place due to the inability of the farmers to pay regular taxes.*********************************************************************************************************</p><p>JAINISM* In the 6 century BC, Buddhism and Jainism emerged as the most important and potent religious reform movements. The kshatriyas reacted strongly against brahiminical dominance and led a movement to dislodge the existing social order dominated by the brahmins. The two important religious mo..</p>
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