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ABSTRACT
The present review deals with the bioactive compounds of the marine non-chordates. The potent
medicinal usage of the bioactive compounds viz. steroids, terpenoids, isoprenoid and non-isoprenoid
compounds, quinones, brominated compounds, nitrogen heterocyclics and nitrogen-sulphur
heterocyclics from marine non-chordates have been compiled. Various literatures survey revealed that
the bioactive compounds isolated in recent past from the marine poriferans, cnidarians, annelids,
arthropods, molluscs and echinoderms could be rich sources of therapeutic agents having antibacterial,
antiinflamatory, anticarcinogenic properties. In overall, the present study will be benefitted to know
global drug discovery researches on bioactive compounds from marine organisms for students,
scholars, scientists, pharmaceutical sector, and government regulating authorities as new challenging
technology in clinical applications through medicines.
1. INTRODUCTION
Marine natural products have attracted the attention to biologists and chemists all over
the world for the last five decades. Approximately 16,000 marine natural products have been
isolated from marine organisms and reported in approximately 6,800 publications as of date.
In addition to these publications there are approximately another 9,000 reports, which cover
syntheses, reviews, biological activity studies, ecological studies etc. on the subject of marine
natural products.
In the animal world non-chordates constitutes an important component of study and the
marine non-chordates comprises the major part. Multicellular non-chordates starting from the
phylum porifera to echinodermata are normally found in the salt water and their ability to live
in this halobiotic enviornment are due to their special adaptations, metabolic activities,
secretions are all different from that of other animals and hence majority of them produce
bioactive substances, which enables them to combat in that harsh environment. All members
of the invertebrates utilize a ‘plethora of substancesin’; their natural immunity ranging from
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International Letters of Natural Sciences Vol 34 43
peptides to alkaloids to trepenoids to steroids for defence and preservation of their natural
integrity.
The ocean is considered to be a source of potential drugs and some of these bioactive
compounds or secondary metabolites have biomedical potential. Oceans comprise 70% of the
earth area and the marine ecosystems represent 95% of the biosphere. 33-34% animal phyla
live in marine environment (Sima and Vetvicka, 2011). The marine life constitutes almost
80% of the world biota (McCarthy and Pomponi, 2004). The diversity of the species is
extraordinary and in the tropical zones there are almost 1000 different species per square
meter. Environmental pressure like competition for space, nutrition and self defence have led
to the production of a diverse array of compounds called the secondary metabolites. These
animals use the secondary metabolites for inter communication between themselves and their
environment. These communication molecules evolved within the scope of symbiotic
interrelationship.
The bioactive compounds generated majorly from marine animals are known as the
secondary metabolites. These could be divided into steroids, terpenoids, isoprenoids,
nonisoprenoids, quinones, brominated compounds, nitrogen heterocyclics, and nitrogen
sulphur heterocyclics. Many of these molecules also represent ancient defence factors.
Bioactive substances formed by marine organisms such as protozoans and invertebrates viz.
poriferans, cnidarians, annelids, arthropods, molluscs and echinoderms have attracted
attention due to their antiviral, antimicrobial, antiprotozoal, antifungal, antihelminthic and
anticancer activities (Zapata and Amemiya, 2000). There are many researches on different
metabolites of unusual structure and exhibiting biological activities (Erickson, 1983; Shimizu,
1993; Faulkner, 2002; Belarbi et al., 2003; Aneiros and Garateix, 2004; Garcia et al., 2007;
Sima and Vetvicka, 2011; Alam et al., 2012; Kiran et al., 2014; Rahaman et al., 2014).
A vast number of bioactive compounds are produced by phylogenetically diverse
organisms that have different and often unpredictable chemical activity and structure. They
are small molecules, generally up to 3000 Daltons. Until the end of the first decennium of this
century more than 15,000 natural compounds have already been isolated from poriferans,
cnidarians, annelids, arthropods, molluscs and echinoderms. These compounds belong to
various families of chemicals. Some of them have exotic structures. Their activities blocks
metaboltic/enzymatic reactions, interrupts the cell cycle, effects phagocytosis and takes part in
cellular killing etc. During the past few years a large number of novel compounds have been
reported (Willams et al. 1989; Pomponi, 1999; Jimeno, 2002). Some of these compounds
have studied clinical /preclinical trials and expected that they can be used as therapeutics in
the near future.
In general, a large number of highly active antitumor compounds have been isolated
from marine invertebrates. The best known examples include eleutherobin from Eleutherobia
family of corals, sarcodictyin from Mediterranean Stolonigeran coral, the bryostatins from
Bryozoan, Bugula neritine, and the dolastatins from the sea hare, Dolabell auriculata (May
et al., 1987; Schmitz et al., 1993). Extracts of marine organisms being examined for
antitumor compounds have been screened in a panel of about 60 human cancer cell lines in
therapeutic areas of leukaemia, breast, ovarian, renal, prostrate, brain, colon, melanoma and
lung cancers. The study of isolation of various chemical(s) as bioactive compounds from
marine non-chordates and their medicinal usage have already been reported earlier
internationally (Bergmann and Feeney, 1950; 1960; Burkholder and Sharma, 1969; Fenical
and McConnel, 1975; Erickson, 1983; May et al., 1987; Willams et al., 1989; Schmitz et al.
1993; Faulker, 1995; Fuesetani, 2000; Towle et al., 2001; Faulkner, 2002; Jimeno, 2002;
Belarbi et al., 2003; Aneiros and Garateix, 2004; McCarthy and Pomponi, 2004; Simmons et
44 Volume 34
al., 2005; Zhang et al., 2006; Garcia et al., 2007; Kuramoto et al., 2008; Laport et al., 2009;
Miller et al., 2010; Sima and Vetvicka, 2011; Alam et al., 2012; Bragadeeswaran et al., 2013;
Kiran et al., 2014; Rahaman et al., 2014). There are also some scattered studies on bioactive
compounds at national level (Chellaram et al., 2004; Santhana Ramasamy and Murugan,
2005; Chellaram et al., 2009; Maripandi et al., 2010; Sivasubramanian et al., 2011; Johnson et
al., 2012; Bragadeeswaran et al., 2013; Dhinakaran and Lipton, 2014; Datta et al., 2014;
Talapatra et al., 2014).
The present review aims to compile from different available literatures on bioactive
compounds isolated from blood, tissues, cells and/or whole body of marine non-chordates that
are of potential medicinal values.
Marine life is fascinating and has great potential for development of drugs. The number
of natural products isolated from marine organisms increases rapidly and now exceeds 18,000
(Marinlit, 2007; Faulkner, 1995; Faulkner, 2002; Proksch and Edrada, 2002). The modern
idea of treatment of human ailment comprises of natural products with unusual structure and
function derived from marine invertebrates. Some of these notable biodynamic agents of
marine origin are cephalosporin, cytosine, saxotoin, didemins etc., which have clinical
importance. The bioactive compounds viz. steroids, terpenoids, isoprenoid and non-
isoprenoid compounds, quinones, brominated compounds, nitrogen heterocyclics and
nitrogen-sulphur heterocyclics from marine non-chordates have compiled. (Table 1). The
compilation of various literatures and study of bioactive compounds and their medicinal
importance from marine non-chordates are as follows:
Sponges are traditionally rich sources of bioactive substances (McConnell et al., 1994).
Even anti-malarial drugs like Manzamines are also reported from marine Sponges (Poriferas).
The pioneering discovery of bioactive compounds from marine sources was the serendipitous
isolation of C-Nucleosides, spongouridine and spongothymidine from Caribbean sponge
Cryptothecaa crypt in early1950s. (Bergmann and Feeney, 1950). These compounds have
potential antiviral activity and their synthetic analog was an anticancer drug (McConnell et
al.,1994). Since, the first report of Manzamine A in 1986 and some 40 related compounds
have been described from more than a dozen of species of Poriferas (Edrada et al., 1996). It
has been reported that Manzamine A has potent antimalarial activity against rodent malarial
parasite Plasmodium berghei in vivo (Ang et al., 2000). These compounds also include a
variety of anticancer drugs like polyhyroxylated lactone, discodermlide isolated from the
Caribbean Sponges Discodermia dissolute (Gunasekera et al., 1991). HTI-286, a synthetic
analog of hemiasterlin (Nieman et al, 2003) originally isolated from a South African Sponge
Hemiasterella minor (Talpir et al., 1994) and soon thereafter from Papua New Guinea Sponge
from Cymbastela sp. (Coleman et al. 1995) and a synthetic analog (E7389) of Halichondrin B
(Towle et al., 2001), which was originally isolated from a Japanese Sponge. There are several
bioactive compounds viz. sterols, terpenoids, phenolic or quinoid, carotenoids etc. from
marine sponges reported for medicinal values. Marine sponges are a good source of unusual
sterols and these sterols have the function on biological membranes. The sulphated and
International Letters of Natural Sciences Vol 34 45
alkaloid sterols have exhibited antimicrobial activity. A bioactive compound, halistanol was
studied by Fusetani et al., (1981) from Halichondria mooriei, also halistanol sulfate from a
marine sponge of the genus Aka (Mukku et al., 2003), halistanol trisulfate, a sulfated steroid
derivative, was isolated from the extracts of two different marine sponges of genus Topsentia
studied by Slate et al., (1995). It was reported by Townsend et al., (1992), the pigmented
human melanoma cell line, MM418, became demelanized when treated continuously with a
nontoxic level of halistanol trisulphate (HTS), a C29 steroidal detergent isolated from a
marine sponge. According to Nakasu et al., (1983), the sterols from Toxadocia zumi inhibited
the growth of two species of bacteria namely Staphylococcus aureus and Bacillus subtitis. A
hydroxyl sterol with unusual features is isolated from Dysidea sp. (Gunasekera and Schmitz,
1983). There are two types of steroidal alkaloids viz. plakinamine A and plakinamine B as
antimicrobial metabolites, were obtained from Plakina sp. and the compound was inhibited
the growth of Staphylococcus aureus and Candida albicans (Rosser and Faulkner, 1984). The
antimicrobial agent siphonodictyal-A and -B and have been isolated by Sullivan et al. (1981;
1983). The compounds viz. arenarol arenarone and illimaquinone from Dysidea arenaria,
puupehenone from Hyrtios eubamma and sesquiterpene phenol from Smenospongia echina
have been obtained by researchers ((Djura et al., 1980; Schmitz et al., 1984). Biologically
active two compounds namely sesquiterpenoid and avarol, which was exhibited antimicrobial
activity and also found active against “AIDS” virus was first isolated from a Mediterranean
sponge Disidea avara (Minale et al., 1974) and later on from an Australian sponge Disidea
sp. (Baker, 1976). Ent-chromazonarol, yet another interesting compound biogenetically
related to avarol has been isolated from the marine porifera Disidea pallescens (Cimino et al.,
1975; Barrero et al., 1999; Ishibashi et al., 2004). Also an interesting group of triprenyl
phenols have been isolated from the red sponge Halichondria panacea (Cimino et al., 1973;
Casapullo et al., 1993; Jaspars et al., 1995). Spongia officinalis, the common bath sponge is a
rich source of terpenoids. Antifungal and antimicrobial activities have been reported in the
tetracyclic furanoditerpenes isolated from sponge S. officinalis. Spongia-13, 14-dien-19-oic
acid (Djerassi, et al., 1979) spongia-13-14-dien-19-al and spongia-13--14-diene are isolated
by Capelle et al., (1980) from the same species diterpenes have also been isolated. Gonzalez
et al., (1984) reported diterpenoids containing a purine or a 9-methyladenine unit (Djerassi, et
al., 1979). These compounds exhibit antimicrobial and Na, K-ATPase inhibitory activities.
According to Funel et al., (2004) novel bicyclic and monocyclic diterpenoids with a 9-
methyladenine unit possessing inhibitory effect on Na, K-ATPase have been isolated from sea
sponge Agelas nakamurai. A series of tricyclic diterpenes having isocyano, hydroxyl,
tetrahydropyranyl and chlorine functions and exhibiting antibiotic activity were isolated from
Acanthella species (Patra et al., 1984; Tsukamoto et al., 2003). Many species of genus
Spongia contain biosynthetically intriguing C21 difuranoterpenes probably derived from
linear sesterterpene tetronic acid. Luffarella variabilis has furnished four sesterterpenoid
antibiotics (De Silva and Scheuer, 1980; 1981). Several tetracarbocyclic sesterterpenes have
been isolated from Cacospongia scalaris (Yasuda and Tada, 1981). The bioactive compound
showed cytotoxicity against the P-388 cell lines (Liu et al., 2004). The compounds from this
sponge also exhibit antifungal and antiinflammatory activities (Roy et al., 2002).
Phyllofenone A and 20,24-diethyl-25-norscalorane sesterterpene with antifungal activity from
sponge Phyllospongia foliascens (Pallas) have been isolated by Kimuchi et al., (1981; 1983).
Sokoloff et al., (1982) have investigated norsesterterpenoid peroxide antibiotics from the Red
Sea sponge Prianos sp. The peroxides strongly inhibit the growth of Gram-positive bacteria
(Crews et al., 1985). Further, several carotenoids have been isolated from marine sponges
(Litchfield et al., 1980; Sliwka et al., 1987; Santoro et al., 1990; Loya et al., 1992; Lysek et
46 Volume 34
al., 2003). Sponges also elaborate unusual compounds from tyrosin and tryptophane.
Brominated tryptamines from Smenospongia sp. exhibited antimicrobial activity (Djura et al.,
1980). Methyl-aplysinopsin from Aplysinopsis reticulate, is a short acting inhibitor of
monoamine oxidase was reported by Taylor et al., (1981). Numerous drugs from marine
sponges have been identified as a source of targeting microtubules (Zhou and Giannakakou,
2005; Miller et al., 2010). The anti-cancer activity of these agents may lie mainly in their
inhibitory effects on spindle microtubule dynamics, rather than in their effects on microtubule
polymer mass (Zhou and Giannakakou, 2005). Substances such asjaspolide, dolastatin,
halichondrin, spongistatin, hemiasterlin, dictyostatin, dis-codermolide, laulimalide, peloruside
A and zampanolide infuence function of the cytoskeleton similar (Kingston, 2009; Saito,
2009). Among marine invertebrates, Porifera (sponges) are potential source of novel bioactive
compounds to provide future drugs against malaria, cancer and a range of viral diseases was
reviewed and documented by (Ravichandran et al., 2007). Sima and Vetvika, (2011) have
documented the clinical use of secondary metabolites for the therapy of cancer from marine
poriferans. Johnson et al., (2012) have studied in vitro antimicrobial activity of marine sponge
Zygomycale sp. collected from Kanyakumari coast (south east coast of India). The sponge
extract was tested against nine human bacterial pathogens and four human fungal pathogens,
and it was revealed that, the extracts showed potent antibacterial activity against bacteria such
as Bacillus megaterium, Klebsiella pneumoniae and Sterptococcus pyogenes and it exhibited
antifungal activity against all pathogenic test strains. Hardoim and Costa, (2014) have
reviewed that several bioactive terpenoids and polyketides have been retrieved from Irciniidae
sponges, but the actual producer (host or symbiont) of these compounds has rarely been
clarified.
Cnidarians are the richest natural sources of prostaglandins, so far discovered in the soft
coral Plexaura hamomala found on Caribbean Sea. Bioactive substances have also been
procured from bryozoans (Carle and Christophersen, 1980).
There has been much interest in the metabolites of jelly fish, sea nettle, the Portuguese
man-of-war and the sea wasp which are widely distributed in warm tropical seas. The
organisms release nematocyst venom from the tentacles which causes painful injuries. The
venoms are generally a complex mixture of enzymes and pain-producing factors. The
nematocyst venom of P. physalis is a mixture of toxic proteins and enzymes, which showed
multiple action including dermonecrosis, neurotoxicity, hemolysis and cardiotoxicity (Carle
and Christophersen, 1980; Banduraga et al., 1982).
Several species of sea anemones produced toxins that are polypeptides or proteins in the
sea coasts of the Andaman and Nicobar islands. The toxins are found very useful tools for
studying the voltage dependent Na+ channels in nerve and cardiac muscle cells. It has been
suggested that coelenterate toxins would be suitable for studies of tumor cell cytolysis in vitro
and in vivo (Fusetani et al., 1981; Kobayashi et al., 1984; Groweiss et al., 1985).
Some of the soft corals that occur in the Andaman and Nicobar Islands are horny
gorgonians, sea fans, the red organ-pipe coral, the blue coral, Helipora sp. and mushroom
coral Fungia sp. The coral Clavularia viridis has yielded cytotoxic steroids, stoloniferones A-
D (Kobayashi et al., 1984). Soft corals were elaborated a large variety of sesquiterpenoids and
diterpenoids. Several of these compounds were reported as toxic. Guaiazulene from the
gorgonian Euplexaura erecta exhibited mild activity against Pseudomonas aeruginosa
(Fusetani et al., 1981). Subergorgic acid, a cardiotoxin is obtained from the pacific gorgonian
International Letters of Natural Sciences Vol 34 47
coral Subergorgia suberosa (Groweiss et al., 1985). The toxin was inhibited neuromuscular
transmission at 0.16 µg/mL in isolated guinea-pig heart assay. Pseudopterolide, an unusual
diterpene with a 12 member ring from the gorgonian Pseudopterogorgia acerosa showed
unusual cytotoxic properties (Banduraga et al., 1982).
The marine bryozoan, Flustra foliacea has yielded several brominated alkaloids called
flustramines division of the fertilized sea urchin eggs (Wright, 1984). The bryozoan
Phidolopora pacifica has yielded phidolopin, a purine derivative largely responsible for high
order of antifungal and antialgal activities (Ayer et al., 1984; Hirota et al., 1985; Avasthi et
al., 1996). Several macrolides like bryostatin-1 and bryostatin-2 were isolated from Bugula
neritina. Some of these metabolites were showed high order of antineoplastic activity (Pettit
et al., 1982; 1983a; b). The compounds such as [2-Hydroxyethyl]dimethyl sulfoxonium ion
acts as an allergen and were isolated from marine bryozoan Alcyonidium gelatinosum (Carle
and Christophersen, 1980).
The glycosides, cervicosides and prostanoid sclaviridenones, from the soft corals
Sinularia cervicornis and Clavularia viridis were shown to have antitumor activity against
human cancer cell lines (Zhang et al., 2006). The polyoxygenated steroids from Alcyonum
patagonicum and another coral species (Nephtea erecta) were represented the most numerous
group of coral diterpenoids, which have mild-to-strong cytotoxicity to the human tumor cell
lines CCRF-CEM and DLD1 (Duh et al., 1998). Another cytotoxic and cytostatic compounds
from soft coral were eleutherobin (Lindel et al., 1997; Long et al., 1998) and sarcodictyin
(Burres et al. 1991; Hamel et al. 1999), which interfered with microtubulins by increasing
polymerization. It was observed and reported by McDaid et al., (1999) that in addition, above-
mentioned natural product was shown a potent cancer cell inhibitor with an IC50 similar to
that of paclitaxel (Taxol®) (10-15 nmol/L), and assays were carried out in the National
Cancer Institute’s 60 cell line panel showed a 100-fold greater potency over the mean
cytotoxicity towards breast, renal, ovarian and lung cancer cell lines. Secondary bioactive
metabolites were also discovered in gorgonians. They are mainly steroids and terpenoids and
several lipid compounds. The strong and selective cytotoxicity was documented for the
oxygenated lactones (menverins) from Menella verrucosa (Li et al., 2008). Furean
sesquiterpenoids from Torilis japonica exhibited signifcant cytotoxicity toward the growth of
A549, HT-29, KB, P-388 and P-388 cells (Park et al., 2006). Sima and Vetvika, (2011) have
documented the clinical use of secondary metabolites for the therapy of cancer from marine
coelenterates. They have documented the clinical use of secondary metabolites for the therapy
of cancer from marine coelenterates. Generally all substances with bioactive activities mainly
steroids, terpenes, and other compounds (e.g., ceramides) were obtained from sea anemones
and corals (Anthozoa). A great number of diterpenoids classifed into the dollabelane,
xenicane, phenylgermacrane, and cembranegroups were showing cytotoxicity against cancer
cell lines isolated from Nepheta sp., also the clavulactones, clavirolides and clavudiols
isolated from Clavularia sp. According to Japanese Foundation for Cancer Research 39 cell
line assay, these compounds were examined for growth-inhibition activities in vitro toward
human cancer cells and reported in the results that moderate cytotoxic activity against human
colorectal adenocarcinoma cells (DLD-1) with an IC50 of 5.0 μg/mL. The lobane diterpenes
and lobane lacatnes, the pacifns from Sinularia sp. and Lobophytum sp. appeared similar
cytotoxicity. A number of diterpenoids of the xenicane groups from Xenia sp. exhibited mild-
to-potent cytotoxic activities against human lung carcinoma (H460) and liver carcinoma
(HepG2) cell lines (Su and Wen, 2011). The cembrane substances mainly from Sinularia
triangular were isolated by Su and Wen, (2011).
48 Volume 34
Several bioactive compounds have also been isolated from marine arthropods. From
marine arthropods, the most remarkable bioactive substance is Limulus Amoebocyte Lysate
(LAL). It is an aqueous extract of blood cells (amoebocyte) from horseshoe crab Limulus
polyphemus. LAL reacts with bacterial endotoxin or lipopolysaccharides (LPS), which is a
membrane component of Gram negative bacteria. The reaction is the basics of LAL test that is
used for the detection and quantification of bacterial endotoxin (Hurley et al., 1991). Fred
Bang reported in 1956 that Gram negative bacteria even if killed will cause the blood of
horseshoe crab to turn into a semisolid mass. It was later recognised that the animal’s blood
cells, mobile cells called amoebocyte, contains granules with clotting factor known as
Coagulogen. In 1970, the US Food and Drug Administration (FDA) approved LAL for testing
drugs, products, and devices that come in contact with blood. Prior to date much slower and
expensive test were done on rabbits for the purpose. The underlying defence mechanism of
the horseshoe crab, a marine arthropod remains to be solved which has survived for millions
of years as a ‘living fossils’. An agglutinin named limulin was discovered in Limulus
polyphemus, which is a sialic acid binding lectin. It was proposed to play some role in host
defence mechanism. However, Indian variety horseshoe crab, Carcinoscorpius rotundacauda
containing sialic acid binding lectin carcinoscorpin, which acts as an opsonising agent like
vertebrate antibody. It is provided higher host resistance for an induced circulatory level and
enhanced rate of phagocytosis for lectin opsonised bacteria thus playing the role of a humoral
factor as in vertebrate-‘C’ reaction protein of vertebrates (Basu et al. 1995). Foreign cell
cytolysis by limulin represents a novel function for a plasma lectin and is the first documented
function for limulin (Armstrong et al., 1996). Armstrong et al., (1998) have reported that in
case of hemolysis, alpha2-macroglobulin was not involved directly when unreacted but
International Letters of Natural Sciences Vol 34 49
A bioactive compound was isolated from the Hawaian mollusk, Elysia rufescens
(Hanmann et al., 1993; 1996) spisulosine, isolated from the marine clam, Spisula polynyma
(Hanmann et al., 1993). Dolatriol, isolated from marine mollusca Dollabella auricularia has
pronounced antileukemic activity. Synthadotin, Soblidotin are two synthetic analogues of
Dolstatin isolated from molluscan species D. auricularia, which are in trial for medicinal
properties.
Several bioactive compounds viz. steroidal, terpenoids, and acetylenic compounds
isolated from nudibranchs and the same compounds were also reported in sponges which
these nudibranchs feed upon (Cimino et al., 1980). The bioactive nucleoside characterised as
1-methyl-isoguanosine has been found in the nudibranch Anisodoris nobilis (Fuhrman et al.,
50 Volume 34
1980; Kim et al., 1981; Grozinger et al., 1983). It is interesting to note that bioactive
compound as N-glycolylneuraminic acid-specific lectin (PAL) purified from an albumin
gland extract of the apple snail, Pila globosa found in freshwater (Swarnakar et al., 1991) that
compound may also found in marine gastropods. A bioactive compound Isoguanosine was
isolated for hypotension and relaxation of smooth muscles in mammals from marine
nudibranch Diaulula sandiegensis (Fuhrman et al., 1981). Another compound
Hexadecylglycerol was isolated from Archidoris montereyensis showed antibacterial activity
in vitro against Staphylococcus aureus and Bacillus subtilis (Gustafson and Andersen, 1985).
It was known that sea-hares accumulate large quantities of metabolites in their digestive gland
and skin. These compounds were believed to originate from the algae, which they feed.
Aplysiatoxin, a toxic metabolite has been isolated both from the Hawaiian sea-hare
Stylocheilus longicauda and also from blue-green alga Lynbrya majusticula on which it feeds
(Moore et al., 1984). Aplysistatin is a well known antileukemic metabolite from the sea-hare
Aplysia angasi (Hoye et al., 1982). The metabolites of Aplysia dactylomela were reported as
cytotoxic and antitumor activity in vivo (Schmitz et al., 1981). The mollusc species Dolabella
auricularia has been reported for yielding several antineoplastic and cytotoxic compounds
named dolastatins. (Pettit et al. 1981; 1982, Harrigan et al. 1998; Poncet et al. 1999; Luesch et
al., 2002). It was reported that marine snails of the family conidae synthesized potent toxins
when they inject into their prey by means of a hollow tooth in order to immobilised their prey.
Few species are known to cause injuries to humans and have proved fatal. The venom of
Conus geographus is most dangerous to man. A bioactive compound striatoxin, a cardiotonic
glycoprotein was obtained from Conus striatus that was reported to have long lasting
isotropic action on guinea-pig left atria (Kobayashi et al., 1982). The bioactive compound,
Zinconitide isolated from a snail, Conus magnus, is licensed by Elan Pharmaceuticals under
the name Prialt and is used for intratracheal treatment for chronic pain. Dollastains are highly
active anti-tumor compounds isolated from a sea slug. In some cases potentially interesting
compounds have been isolated from molluscs, a HIV virus-inhibiting compound from the
green mussel Perna viridis has been studied and patented (Berge et al., 1997). Kelletinin-I and
II isolated from marine mollusc, Kelletia kelletii inhibited the growth of Bacillus subtilis and
L1 leukemia cells as antibacterial and anticancer agents (Fuhrman et al., 1981; Tymiak and
Rinehart, 1983). It was reported that Surugatoxin and neosurugatoxin were isolated from
Japanese ivory shell, Babylonia japonica (Kosuge et al., 1981; 1982) and it was found that the
antinicotinic activity of the latter is found to be 100 times that of the former. The antibiotic
diemensin A and diemensin B was found in another mollusc species Siphonaria diemensis
(Kosuge et al., 1982). The former was inhibited the growth of Staphylococcus aureus and
Bacillus subtilis at 1 µg/disc and 5 µg/disc, respectively. It was also reported to inhibits cell
divisions in the fertilized sea-urchin egg assay at 1 µg/mL. A potential polysaccharide with
potent antibacterial and antifungal activity was extracted from the cuttle bone of Sepia
aculeata and Sepia brevimana. Polysaccharide isolated from these cephalopod species were
studied for their antibacterial and antifungal activity against nine bacterial species (Bacillus
subtilis, Escherichia coli, Klebsiella pneumoniae, Vibrio cholerae, Vibrio
parahaemolyticus, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhii and
Shigella sp.) and four fungal species (Candida sp., Rhizopus sp., Aspergillus flavus and
Aspergillus fumigatus) pathogens at different concentrations such as 25, 50, 75 and 100%
against control. The activities were found to be increasing with the increasing concentration
of the extracts. No antibacterial activity was recorded against V. cholerae in all concentrations
of S. brevimana. In S. aculeata, maximum and minimum activity was recorded against E. coli,
but in S. brevimana the highest and lowest activity was recorded against P. aeruginosa and E.
coli, respectively. In the antifungal activity study, the highest and lowest inhibition zones
were noted against A. flavus, Candida sp. and A. fumigates and Rhizopus sp. respectively, but
in S. brevimana, maximum and minimum activity were observed against A. flavus and A
International Letters of Natural Sciences Vol 34 51
cucumbers have been studied (Stonik, 1986). Many cerebrosides, pyrimidine nucleosides,
thymine deoxyriboside and uracil deoxyribose have been isolated from the starfish
Acanthester planei (Komori et al., 1980).
Pedicellaria of some species of sea-urchins contained toxic substances. Extract of
Toxopneustes pileolus causes histamine release from isolated smooth muscles (Kimura, and
Nakgawa, 1980). The extract of the organism produced contraction of the longitudinal
muscles of isolated guinea-pig ileum at a concentration of 3 × 10–8g/mL. There are two types
of echinoderms namely Lytechinus variegates and Strongylocentrotus droebachiensis have
yielded for antineoplastic glycoproteins (Pettit et al., 1981a; b). Linhardt et al., (1990) have
reported that low molecular weight sulphated polysaccharides were noted from sea cucumbers
with efficient anticoagulant activities and several pharmacological properties. The
chondroiton and glucosamine components of holothuria were reported to be important
cartilage building blocks and other bio activities including anti-inflammatory and antitumor
activity properties (Herecia and Ubeda, 1998).
The bioactive compounds were reported to act as the chemokine receptor subtype-5
(CCR5) with possible anti-HIV activity from the sea cucumber species, Telenata ananas
(Hegde et al., 2002). Bioactive compounds isolated from sea cucumber species S. liouvillei
containing chondroitin sulphate (the polysaccharides) that exhibits antiviral activity to inhibit
human immuno deficiency virus (HIV) infection (Chen, 2003). Fuscocineroside C bioactive
compound atriterpene glycoside was obtained from sea cucumber Holothuria fuscocinerea
that showed cytotoxic nature against human cancer cells (Zhang et al., 2006). According to
Zou et al., (2005), Intercedenside D–I isolated a cytotoxic triterpene glycoside from the sea
cucumber Mensamaria intercedens a marine natural product inhibited proliferation of several
human cancer cell lines. Wu et al., (2006) have studied that Hillaside C a triterpene derived
from sea cucumber Holothuria hilla inhibited the growth of human leukemia, breast and
colon cancer cells invitro in a dose and time-dependent manner by a mechanism that required
induction of apoptosis and the concomitant reduction of the apoptosis-suppressing protein
Bcl-effect. The bioactive compounds as steroid glycosides are a class of wide spread natural
products having marine origins. Spirostan and furostansteroid saponins, pregnane glycosides
have a potential to be used as cancer therapies. Structurally, these glycosides exhibit a
moderate cytotoxicity against human leukemia cell lines (Prassas and Diamandis, 2008). The
extract LPS obtained from Stichopus japonicus induced inflammatory response via blocks the
MAPK signalling pathway inmurine macrophages, showed invitro with anti-inflammatory
potential Himayaa et al., (2010). In recent findings, Rahman et al., (2014) reported that many
species of sea urchin male and female gonads are rich in valuable bioactive compounds viz.
polyunsaturated fatty acids (PUFAs) and β-carotene. PUFAs, especially eicosapentaenoic acid
and docosahexaenoic acid, have significant preventive effects on arrhythmia, cardiovascular
diseases and cancer. β-Carotene and some xanthophylls have strong pro-vitamin A activity
and can be used to prevent tumor development and light sensitivity. The sea cucumber
(Holothuriaatra) extracts have been evaluated for the presence of bioactive compounds and
various biological activities. The methanol extracts showed antiproliferative activities against
the Hela and MCF-7 cell lines. Similarly the inhibitory effects of Herpes simplex virus 1 and
2 cells were detected using the plaque reduction assay. The extracts of H. atra were purified
using the silica gel column chromatography and the active fractions showed antimicrobial
activity. The studies were carried out on Staphylococcus aureus MTCC737, E. coli
MTCC443, Klebsiella pneumonia MTCC109, Listeria monocytogenes MTCC1143, and
Serratia liquefaciens MTCC3039 (Dhinakaran and Lipton, 2014).
International Letters of Natural Sciences Vol 34 53
3. CONCLUSIONS
The marine biota has its vastness of living organisms along with their multiplicity and
biodiversity. It provides an immense source of unique life with many special characteristics.
Life in fact, first originated in water hence, the marine life had an ample time to evolve and
flourish in its own way showing its diversity and variety. This marine organism has numerous
ways to combat the intrinsic, extrinsic and environmental factors. They have developed
morphological, physiological and biochemical techniques to save themselves in this
environment. Hence, the bioactive substances produced by them are in one way unique and
essential for their survival. These bioactive substances are utilised by them in their various
spheres of living like, growth, reproduction, communication, protection, defence, locomotion
etc which have complex structural composition and found to have functional significance to
humans. Thus marine organism has served as a source of medicine and pharmaceutical since
ancient times. The body extracts of various marine organisms have cured various diseases
which researchers have tried to study from various angles. The structure and mode of action
of few bioactive compounds become known to the medical world. Numerous pharmaceutical
companies are involved in solving new actions of bioactive compounds from marine sources.
Although no major therapeutic drugs has yet been developed from the sea, but reports of anti-
cancer, anti-inflammatory, anti-microbial wound healers are known.
Drug discoveries from marine non-chordates have an important research field since
decades. Currently, interest in evaluating marine invertebrate products, with the aim of
obtaining new potential disease preventive drugs with few side effects, is still growing. In
many cases, the bioactive compounds from marine organisms are difficult to obtain in
sufficient amounts and researchers, therefore, have to start mimicry mother nature for
preparation of synthetic compounds or drugs.
The rich diversity in bioactive compounds from invertebrates have provided
molecules that interfere with the prevention of a disease at many different points, which
increase the chances of developing selective drugs against specific disease(s). Marine
invertebrates have provided many examples of novel secondary metabolites that possess
varied chemical status and potent antimalarial, antiinflamatory, anticarcinogenic,
antibacterial, antifungal etc. activities (Table 1).
The Sunderban deltatic region of India has a unique not found elsewhere in the world.
Future studies on mangrove biota may serve as a rich source of information as well as
pharmaceuticals significance. In this context recent finding with P. archuata may usher a new
field of processing bioactive substances from marine invertebrate available in Sunderban
deltatic region. It is also very important to know the presence of bioactive compounds in
fiddler crab species inhabited in the same geographical region and/or other mangrove area.
Marine natural products also provide a novel and rich source of chemical diversity
that can contribute to design and development of new and potentially useful therapeutic
drugs. The data from available literatures reveal that the marine ecosystem is not only
the resources to discover various bioactive agents but also an avenue to identify new
cellular targets for drug discovery. A proactive interaction among research scholars, scientists,
pharmaceutical sector, and government regulating authorities is important to the incorporation
of this challenging new bioactive agent in clinical applications.
54 Volume 34
Table 1. The most important bioactive compounds isolated from marine non-chordates.
Marine sources
Major bioactive compounds Disease prevention
(Major phylum)
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