Novel Medicinal Agents from Marine Source

Medicinally important marine organisms, Sponges, Corals, ALgae, Sea cucumbers

1. Novel Medicinal Agents from Marine Sources By Dr Gana Manjusha Kondepudi Associate Professor Vignan Institute of Pharmaceutical Technology

2. The ocean contains more than 200,000 described species of invertebrates and algae. Marine plants, animals, and microbes produce compounds that have potential as pharmaceutical s. These " secondary metabolites ," chemicals that are not needed by the organism for basic or primary metabolic processes, are believed to confer some evolutionary advantage.

3. Many of these plants and animals live in densely populated habitats are non-motile and have only primitive immune systems, they have evolved chemical compounds to help defend against predators, to attract or inhibit other organisms from settling or growing on them, and to provide chemical cues to synchronize reproduction among organisms that expel their eggs and sperm into the water.

4. For example, many natural products have been identified that inhibit cell division , the process that is the primary target of many anti-cancer drugs. The marine environment became a focus of natural products drug discovery research because of its relatively unexplored biodiversity compared to terrestrial environments.

5. The potential of marine natural products as pharmaceuticals was introduced by the pioneering work of Bergmann in the 1950s , which led to the only two marine-derived pharmaceuticals that are clinically available today. The anticancer drug, Ara -C , is used to treat acute myelocytic leukemia and non-Hodgkin's lymphoma. The antiviral drug, Ara -A , is used for the treatment of herpes infections Both are derived from nucleosides isolated from a shallow-water marine sponge collected off the coast of Florida.

6. Marine sponges are among the most prolific sources of diverse chemical compounds with therapeutic potential . Of the more than 5000 chemical compounds derived from marine organisms, more than 30% have been isolated from sponges.

7. Other marine sources of bioactive molecules with therapeutic potential are bryozoans ascidians molluscs cnidarians, algae

8. These bioactive molecules possess activities

9. CARDIOVASCULAR ACTIVE SUBSTANCES i ) Anthopluerins : These are the group of peptides obtained from coelenterates viz. Anthopleura xanthogrammica giving type A and type B (AP-A and AP-B) and Anthopleura elegantissima giving type C (AP-C). AP-A shows positive inotropic action without an effect on Na + K + ATPase pump.

10. CARDIOVASCULAR ACTIVE SUBSTANCES ii) Eptatretin : It is found in the aneural bronchial hearts of Pacific hogfish Viz Eptatretus stoutii . It is a potent cardiac stimulant with direct stimulant action on mammalian myocardium which is compatible to adrenaline.

11. iii) Laminine : A marine algae Laminaria angustata Gives this basic amino acid compound with hypotensive effects. iv) D (-) Octopamine : It produces adrenergic and cardiovascular response and is found in Octopus macropus , O.vulgaris , Eledone moschata .

12. v) Saxitoxin : It shows a hypotensive effect and is found in butter clam i.e. Saxidomus giganteus , California mussel, Mytilus Californianus .

13. vi) Autonomium : This compound has Isosteric structure of adrenaline and acetylcholine and is found in Verongia fistularis . It produces both alpha and beta adrenergic effects and also exhibits cholinergic activity. This compound shows CNS stimulant effects in mice exhibited by significant increase in spontaneous motor activity. Due to both adrenergic and cholinergic effects, this compound may proven to be useful in regulating the behaviour of heart.

14. ATX- II : this is one of the polypeptides found in sea anemones. Like anthopluerins , it also shows portent and dose-dependent cardiotonic response in mammalian heart preparations. It is suggested that the cardiotonic effect is due to indirect action on the pump activity e induced by increased sodium transport as a result of a delayed inactivation of fast sodium current .

15. Besides ATX- II and anthopluerins , various polypeptides have been obtained from different sea anemones like Condylactis gigantea with 195 amino acid residue peptide and hemolytic action in rabbits, Parasicyonis actionstoloides with a neurotoxic peptide and very less number of amino acids and Actinia equina with 147 amino acids exhibiting bradycardia rapid hypertension and respiratory arrest in the intact rat,

16. Holothurins and asterosaponins : these are marine saponins holothurins contain triterpenoid moiety as aglycone and asterosaponins have steroidal aglycone . Holothurins are present in sea cucumbers, belonging to the family Holothuridae . Holothurins have cardiotonic action. They show hemolytic activity. Holoxins like holotoxin A, B and C are desulphated holothurins nad possess antifungal activity.

17. Asterosaponins which are obtained from Star fishes of family asteroidae are toxic to various Marine organisms they exert different pharmacological actions like hemolytic anti inflammatory hypertensive and analgesic effects and also cytolytic action due to interference in protein metabolism and neuromuscular blocking effects. They are inhibitors of ATPase , but holothurins are potent in this comparison.

18. Spongosine : chemically it is a nucleoside ( methoxy derivative of adenosine) it is found in the extract of Caribbean sponge Crypotethia crypts . It reduces both the rate and the force of contractions of heart . Like spongosine many nucleotides have been reported from Marine sources like doridosine (hypertensive and hypothermic) from Anisodoris nobili s,5-deoxy-5 iodotubericidin ( muscle relaxant, hypothermic and potent inhibitor of adenosine kinase ) from red algae Hypnea valentine. Eledosin : it is a powerful hypertensive compound obtained from posterior salivary glands of cephalopod Eledone moschata . It shows strong vasodilator effects.

19. Laminine Spongosine

20. Cytotoxic anticancer compounds Ara -C It is a 1-alpha-D-arabinofuranosyl cytosine or cytosine arabinoside . It is obtained as a synthetic compound based on the knowledge of naturally occurring moieties present in Caribbean sponges viz spongosine , spongouridine . Ara -C is used in the treatment of acute myelogenous leukaemia and human acute leukaemia . It is Active against Erlich carcinoma, sarcoma-180 and L-1210 leukaemia in mice .

21. Ara -C Crassin Acetate Sinularin

22. Crassin acetate: It is a member of cembranoids which are cyclic diterpenes obtain from soft corals . Crassin acetate is obtained from Carribbean gorgonian Pseudoplexaura porosa , which is cytotoxic to human leukemic and Hela cells in vitro. Among the various cembranoids , a soft coral Sinularia flexibilis gives sinularin , dihydrosinularin and sinulariolide .

23. Many compounds with antitumor and immunosuppressant compounds have been reported Ex: geranyl hydroquinone ( Cytotoxic to leukemia and mammary carcinoma) from chloroform extract of Aplidium speices , Aplysistatin (Anti leukemic) from sea hare Aplysia angasi ; halitoxin (Anti tumor) from a sponge Haliclona virdis ; didemnins A, B and C (Potent inhibitors of leukemic cells in vitro ) from Caribbean tunicate Trididemnum species.

24. Geranyl hydroquinone Aplysistatin

25. Anti Microbial Compounds A large number of antimicrobial compounds have been detected from marine organisms like sea cucumbers, marine algae, sea hare, gorgonian corals and red algae.

26. Antibiotic Compounds

27. Anti-inflammatory and antispasmodic agents: 1. Manoalide : It is obtained from the Luffariella variables . It is act by direct inactivation of phospholipase A2, which is present in some neurotoxins and also has a role in synthesis of PGs in humans. Also has analgesic and selective anti-inflammatory activity. 2. Flaxibilide : It is a diterpenoid obtained from the Sinularia flexibilis .

28. 3. Flustramine A and B: It is obtained from the Flustra foliaceal (Swedish marine moss animal). It is used as muscle relaxant. 4. Tetradoxin : It is obtained from the puffer fishes Spherides rubripes , (liver and ovaries). It is used as strong antispasmodic. 5. Dendalone-3-hydroxy butyrate: It is obtained from the Phyllospongia dendyi . It is used as anti-inflammatory agent.

29. Antiviral compounds: 1 . Ara -A: It is obtained from the sponge, Tethya crypta . 2. Avarol and Avarone : It is obtained from the sponge, Disidea avara . These compounds inhibit the immuno -deficient virus, have high therapeutic indicates and the ability to cross blood brain barrier. The compounds have potential use in the treatment of AIDS .

30. 3. Eudostomin -A: It obtained from the Eudostoma olivaceum . 4. Patellazole -B: It obtained from the ascidian lissocilium patella. 5. Oppositol : It is obtained from laurencia suboppostia .

31. Antiparasitic compounds: 1 . Domoic acid: It is obtained from the red algae, chondria armata . It is used as anthelmintic . 2. α- kainic acid: It is obtained from the red algae, digenia simplex. It is used broad spectrum anthelmintic . It is effective against parasitic roundworm, whip worm and tape worm. 3. Cucummechinoside -F: It is obtained from the sea cucumber. It is used as antiprotozoal activity.

32. 4. Bengamide -F: It is obtained from the sponges, nudibranch and a zoanthid . 5. Laminine : It is obtained from Laminaria angustata . It is use as an anthelmintic as well as smooth muscle relaxant.

33. Anticoagulant agents: 1. Carrageenan : It is obtained from the Chondrus , Euchauma and Gigrtina . It is reported anticoagulant activity. 2. Galaxtan sulphuric acid: It is obtained from the Iridaea laminariodes . 3. Fucoidan : It is obtained from the Fucus vesiculosus , polyides rotundus .

34. MARINE TOXINS

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