Middle-East Joumal of Scientific Research 5(6): 514-519, 2010 ISSN1990-9233 C IDOSI Publications, 2010 Marine Organisms as Potential Supply for Drug Finding- A Review Study 'P. Satheeshkumar, 'Anisa Basheer Khan and2D. Senthilkumar Department of Ecology and Environmental Sciences. Pondicherry Central University, Puducherry, 605104- India Department of Zoology, Kandaswamy Kandar Arts and Science College, Paramathy-Velur, Tamilnadu, 638181-India Abstract: Oceans are a source of a large group of structurally unique natural products that are mainly found in invertebrates such as sponges, tunicates, bryozoans and molluscs. This diversity has been the source of unique chemical compounds with the potential for industrial development as pharmaceuticals, cosmetics, nutritional supplements, molecular probes, fine chemicals and agrochemicals. In recent years, a significant number of novel metabolites with potent pharmacological properties have been revealed from the marine organisms. At the same time as the marine world offers an extremely well-off source for novel compounds, it also represents a great challenge that requires inputs from various scientific areas to bring the marine chemical diversity up to its therapeutic potential. This review highlights several marine natural products and their synthetic derivatives that are currently undergoing clinical evaluation. Key words: Drugs. Marine organisms. Invertebrates INTRODUCTION sources of novel biologically active agents only began in earnest in the mid-1970s. These studies have clearly The world's oceans, covering more than 70 % of the demonstrated that the marine environment is a rich source earth's surface, represent an enormous resource for the of bioactive compounds, many of which belong to totally discovery of potential chemotherapeutic agents. The novel chemical classes not found in terrestrial sources greater part of the earth surface is covered by the [2]. The interest in nature as a source of potential seas and oceans, which contain about 5, 00,000 species of chemotherapeutic agents continues [3]. The marine marine organisms. All but two of the 28 major animal phyla microorganisms, seaweeds, soft corals, fungus, sponges, are represented in aquatic environments, with eight being bryozoans, tunicates, annelids, holothurians, molluscs, exclusively aquatic, mainly marine [1]. While marine echinoderms have all been reported to be a source of organisms do not have a significant history of use in bioactive molecules (acetogenins, polyketides, terpenes, traditional medicine, the ancient Phoenicians employed alkaloids, peptides and many compounds of mixed a chemical secretion from marine mollusks to produce biosynthesis). purple dyes for woollen cloth and seaweeds have long been used to fertilize the soil. First notable discovery of MARINE NATURAL PRODUCTS biologically active compounds from marine sources was the serendipitous isolation of the C-nucleosides Marine life is fascinating and is considered to have spongouridine and spongothymidine, from the Caribbean great potential for its intrinsic value as well as for the sponge, Cryptotheca crypta, in the early 1950s. These development of new drugs. Earlier studies on chemistry compounds were found to possess antiviral activity of marine natural products were limited to the isolation, and synthetic analog studies eventually led to the structure elucidation and phytogenetic relationship of development of cytosine arabinoside (Ara-C) as a specific substances, such as quinonoid pigment and clinically useful anticancer agent approximately 15 years sterol present in various marine organisms. Now this field later [1], together with Ara-A as an antiviral agent. The attracted the attention of not only the natural product systematic investigation of marine environments as chemists, but also those of marine biologists, biochemists, Corresponding Author: P. Satheeshkumar, Department of Ecology and Environmental Sciences, Pondicherry Central University, Puducherry, 605104- India, E-mail: revathysathish86@gmail.com 514
Middle-East J.Set.Res.5():514-5192010 oharmacologists ete The invention of the acalung and DIBROMO-6(3.4 tribromo pyrrole-2vl)Phenol:Highly the advent of new technology in the past few decades led brominated pyrrole phenol possessing antibiotic to the awareness that the oceans may be a new frontier properties,from marine Pseudomonas bromoutilis of biomedical research and key to cure of many dreaded Cephalosporins:Discovered in the 50's from a marine diseases number of natu ospon has le to es rapidl 5,6A new comp aced fro 1 Drugs from marine sp s:Microbiologists are highly ges ascidians hrvo ans and molluscs and some them are cuenty in clinical trials [7].Research into the enormous amounts of microorganisms.They can be pharmacological properties of marine natural products has considered asmicrobial fermenters'that hold a largely led to the discovery of many potently active agents untapped potential for therapeutics.Sponges are considered worthy of clinical application.The marine traditionally a rich source of bioactive compounds in a environment variety logical screens [I]and a numbe are in develop cts [8]Th ted lac is tha of the Caribbe ytotoxic evelic and linear p tides dolastatins Due 286 a analoe of hemiasterlin 1 to its potency and mechanism of action.dolastatin 10.a isolated from a south african sponge Hemiasterello linear dersipeptide which was shown to be a tubulin minor [12]and soon thereafter from a Papua New Guinea interactive agent.entered Phase I clinical trials in the sponge from Cybastela [13]and a synthetic analog 1990s and progressed through to Phase II trials as a single (E7389)of halichondrin B [14].which was originally agent,but has lack of significan As ey from ten th TZT-1027 (Auistatin PE d fr linical trials in e nd the Inited sto T9] uth isla The modem concent for the treatment of buman ailn ssa cantharella and.389 a synthetic omprises natural roducts with unusual structures and analog of bengamide a isolated from jaspis of coraciac functions derived from marine plants and animals.The advanced into clinical trials,but was dropped due to lack arious biodvnamic agents isolated from marine origin of efficacy [6,9].Avarol and Avarone Isolated from been developed in recent years.Some of the sponge. Diced avara.inhibit immunodeficiency virus. orin,Cytosine,S nigh therapeutic indices and the to cros etc.,are y.T BOL 2. drugs rful 14 and pon n killer Sno Drues from Marine Micro Oreanism and from carribean (West indies)s rynta has Phytopplankton:Numerous bioactive compounds of shown promising anti-tumor and antiviral activities invertebrate origin are in fact microbial metabolites Spongouridine Isolated from Carribean (West Indies originating from dietary.commensalic or endosymbiotic sponge,C.crypta has shown promising anti-tumor and microorganisms.Istamycin A and B.Isolated from marin antiviral sponge Streptomyces lenjimariensis against dve an can fight the Al used in the to as [15] 515
Middle-East 1.Sci.Res..5 (6):514-519.2010 and gra ative bac was modelled based on sp 1231.How most fish c-helical p ptides are m or spongouridine.Ara-A is the first spong -derived of the piscidin family,which include the antiviral compound in the market.Polyketide Calyculin A and piseidins [20]Pleurocidins are 25-residue peptides (a selective inhibitor of protein phosphatise 1.isolated first isolated from the skin mucus of winter flounder. Manoalide (a poten id Drugs from Echinoderms:Marine-derived cor ant protein phosphatises and 2 tively isolated from ecteinascidin 743 isolated from the Caribbean ascidian Luffariella variabilis and Halichondria okadai has Ecteinaseidia turbinata [25].aplidine,the dehydro reached the market undergoing from basic research to analoe of didemnin b.isolated from the Caribbean long phases of clinical study [16,17]. solidum [26].Many cytotoxic of th nterest Drugs them ha are the exhibit anti-Hy and antiinfluenza activity [gl kainic Cystodvtes).HOLOTHURINS.Toxie tri Acid a valuable antibelmintic used clinically in japan terpenoid elvcosides.obtained from sea cucumbers against parasitic roundworm,tapeworm isolated from Actinopyga agassizi are found to inhibit the growth of namely Digene Dom sarcoma and aden sola B,ha ve been - Sulfatad found to non-immune inflammatory response eg. rat paw odema,has also Drugs from Corals:Prostaglandins.(1 5-epi-PGA2 acetate been injected into sinovia l fluid of animals to produce 15 S PGA2)The richest natural source of anti-inflammatory drugs. Nere toxin,A mumbe prostag landins,s far discovered in the soft coral alogenated ated from I ine red algae in the n se ri lich ides PGE2 which s.has plant growth similar to indole auxins sp.Bugula neritina and soft coral compounds,diterpene elycoside 'Eleutherobin'and Pyrrole alkaloid alkaloid Drugs from Fish:Squalamine,isolated from the com Lamellarin D while. anti-inflammatory collecte off th 'OAS-10 whic c de opterisone A are the hope of new effective m Drugs from Molluses:Kahalalide F.isolated from the addition isolated from liver of puffer fish,po Hawaian mollusk.Elysia rufescens [27,28].spisulosine cardiovascular activity. Alpha-helical amphipathic solated from the marine clam,Spisula polynyma [29 are ery commo in fish as re Dolatriol,Isolated from marine Dollabell antile 11 ad fo Moses sole pardachin tug on the hasis of in trials Alkvlamino alcohol ES-2s (Spisuloaine their cytotoxic,pore-forming activitie [2122].Pardaxins isolated from Mactromeris polynyma is another were originally described as toxins with anti-predatory compound in preclinical trial,molecular target of this function but subsequently they have been found to be molluscan compound is Rho (GTP-bp). 516
Middle-East J.Set.Res.5():514-519.2010 The high potency of cone snail venoms has inspired for human health and welfare but also for marine ecoloo pharmacologists to investigate their potential use as [36].These entities are the sources of new leads for adiuncts in anaesthesia. antiepileptic. cardiac and atment of many dis ease such as cancer, AIDS antipsychotic drugs.More than 100 patents and patent con large variety of vira the st 37. al of Indian wealth way back in late 1560 Such efforts were launched Pharmaceuticals under the pame Prialt and is used for in India only in the last decade with prestigious intratracheal treatment for chronic pain. Lungbya nstitutions (Nationa Centre for Ocean Information majuscule was recognized as the source of aplysia toxin FRI.CDRI.NIO)fiuding found in sea slug Aplysia [30].Similarly,a serves of sed their RD highly active antitumor compounds,dollastains ins olate ing by 00%in tit's group are considered to b the past 4 years [24).however,they still spend only one tenth of their revenues on r&d ainst 20%by western sed on the potentially large health benefit Drugs from Annelids:Three novel AMPs have been 0 an purified from marine worms.Two isoforms of the AMP. arenicin.have been purified from the immunecells of the e biomedical tha lueworm.Arenicola marina [31].Th dhRph and the all-too-obvious limitations of our laboratories [38] ing (31 In conclusion study of marine organisms tor ther kill E pote an imp ich and vas permeabilization [32].A second annelid peptide,named Indian coast in the form estuaries creeks deep seas and perinerin,has be ified from the clamworm.Perinereis aibuhitensis [33].Finally.the most recent AMP to be continental shelf is potential useful for research in the ated fr stin purified fro area of marine drug development and exciting new frontier of scientific discovery and economic opportumty es n hedistins ACKNOWLEDGEMENT active gainst Gram and Gram negative bacteria. Authors thank the University Grants Commission Go of Ind for the h Drugs from Other Organism:Bryostatins,A group of ank the aut Pondicherry macrolide known as bryostatins,isolated from Buguld nerie mall-cal REFERENCES Skeleto bronchopulmonary carcinoma line NSCLCN6)[35]. Saclike filter feeder tunicates have been reported to be an Mo Ce .R.E.Longley and FE. Koehn 19 The importent source in drug t Boston.V.P.Gullo.(Eds.).pp 109.174 2. Carte.B.K1996.Biomedical Potential of Marine om 1 Natural Products.Biosciences,pp:271-286 tide Vitile D 3. Newman.D. M.Snader,2000 amide'from Diason ata are G.M.Cragg and a few tunicate compounds in anticancer preclinical or 4 Mar lit Vor arine literatu clinical trials datahase produced and maintained hy the Study of marine organisms is a discipline,which Department of Chemistry,University of Canterbury endeavours to identify and de cipher the trout New Zealand (www.chem.canterbury.ac.nz/marinlit regarding not only sustainable exploitation of marine life marinlit.shtml). 517
Middle-East J.Sci.Res.,(6):514-519.2010 5.Faulkner,D.J,0000.Mari produets.Nature Produet Reports.19:1 17.Lombardo,D.and E.A.Dennis,1985.Cobra veno alida 6.Proksch.P.and W.E.G.Muller,2006.Frontiers in of phospholipase inhibitor.J.Biological Marine Biotechnology.Horizon Bioscience: emistry.260:7234.7240 Norfolk,U.K. 18.Hao,D.,LA.Hammond,S.G.Eckhardt,A.Patnaik 7.Proksch.P.and RA.Edrada Ebel,002.Drugs fron CH Takimoto,G.H.Schwantz,A.D.Goetz A.W Tolcher.HA. McCreery,K.Mamun gy and 125134 I an 8.Carte,B.K.0000.Biomedical Potential of Marine Natural Products.Biosciences,pp:271-286. 9.Newmanm.D.J.and Cragg.2004.In Drug Discovery. 19 Man Cuevas Preventive Medicine. R.Garcia-Nieto. E.Marco and F.Gago. 2001 Adva ces in the emain,(Eds.)Humana Press Chemistry and Phammacology of Ecteinascidins.A Promising New Class of Anticancer Agents Current Medicinal Chemistry-Anti-Cancer Agents. GK.Schulte.1991.Dis polyhydroxylated lactone from the marine sponge :25 276. oluta lerratum to document cited ir 20.Smith and J.M.O. Femandes 2009.Nam mmia dis nnate systen CA 1139):75187b].J.Organic Chemistry,56:1346 11.Nieman A..JE Coleman,D Wallace,E.Pie Eds Science Publisher m, erge Enfield NH USA 1-241-275 Nature 21.Laz vici P N Primor and I M Loe 1986 Analogues 66183.109 Purification and pore-forming activity of two 12.Talpir,R..Y.Benayahu,Y.Kashman and L.Pannell polypeptides from the secretion of the Red Sea Schlever.1994.Hemiasterlin and geodiamolide TA. Moses sole (Pardachirus marmoratus)J.Biological ●hem1sry,26:1670416713 two new cytotoxic peptides from the marine sponge 453-445 minor (Kirkpatrick).Tetrahedron Letter 22.Thompson,S.A. Tachibana, K.Nakanishi 198 13 Cole defense RJ.Andersen Allen.1995.Cytotoxic p tides from the marine sponge Cymbastela sp.Tetrahedron 233.341.243 Letter.51:10653-10662 23.Oren,Z.and Y.Shai,1996.A class of highly 14.Towle M.J K.A.Salvato,J.Budrow,B.F.Wels, antibacterial peptides derived from pardaxin a pore forming peptide isolated from Moses sole fish Zhen MH Pardachirus Euroupean D Biochemistry.237:303-310. D A O 24.Cole. A nd P 1997. Diamond B A Littlefield 2001 In vitro and In vivo pleuro Anticancer Activities of Synthetic Macrocyclic Ketone Analogues of Halichondrin B Cancer Res. 1.1g.12013 1:1013-102 15 25.Sakai.R..KL Rinehart.V.Kishore.B.Kundu G Faireloth IB Gloer IR Camney M Manikoshi F.Sun,R.G.Hughes,J.R.D.Garcia-Gravalos Garcia de Quesada,G.R.Wilson and A Takai and N RM.Heid 199.Structure-Activity Relationships Fusetani,2002.Insight into Binding of Calyculin A of the Didemnins.J.Medicinal Chemistry, to Protein Phosphatase.Chemical Biol..9:309-319 39.28192834 518
Middle-EastJ.Set.Res.5(6):514-519,2010 26.Manuel Martinez-Garcia,Marta Diaz-Valdes,Alfonso 32.Ovchinnikova,T.V.,G.M.Aleshina,S.V.Balandin, nos-Espla. Nelida Salvador Patricia l AD ML Eduardo L ba and Josefa Anton 2007 AA.Ta吗 of the dellechiajei Ag and V.N.Ko Tumor of the Involv and primary tw Associated the on of of a novel an haeta Arenicola marina. 27 33. Pan,.Ge.1.Han and T.Zheng00 Elysia rufescens and the green alga Bryopsis sp.J. Perinerin,a novel antimicrobial peptide purifie American Chemical Scoiety,115:5825-5826. from the clamworm Perinereis aibuhitensis Grube 28.Hamann,M.T C.S.Otto,P.J.Scheuer and and its partial characterization.J.Biochemistry, D.C.Dunbar,1996.Kahalalides:Bioactive Peptides 135:297-304. from a Marine Mollusk Elysia rufescens and Its Algal 34.Tasiemski,A.,D.Schikorski,F.Le Marrec-Croq Diet Bryopsis sp.J.Organic Chemistry,61:6594-6600 C.Pontoire-Van Camp,C.Boidin-Wichlacz and 29.Cuadros,R.,E.Montejo de Garcini,F.Wandosell, Sautiere,2007.Hedistin A novel antimicrobial G.Faircloth.IM Fernandez-Sousa and I Avila 2000 peptide containing bromotryptophan constitutively The marine compound spisulosine,an inhibitor of cell expressed in the NK cells-like of the marine annelid proliferation,promotes the disassembly of actin Nereis diversicolor.Developmental and Comparative stress fibers Cancer Letter 152.23-29 mmunol,.31:749-762 30.Berge.J.P..N.Bourgougnon,D.Carbonnelle.V.Le 35.Jain,R.and S.N.Sonawane.2008.Mandrekar. Bert.C.Tomasoni.P.Durand and C.Roussakis.1997 Marine organisms:Potential source for drug Antiproliferative effects of an organic extract from very.Current Sci.94:292 the marine diatom skeleto ostatum ao. st 36.Jain.R.and A.Tiwari. 2007.S mall-cell bronchop ma line onges:An rtebrate of bioactive potential (NSCLC-N6).Antic Res,17:2115-2120 93444.445 M Kash 37.Mashelka and T.No R.A.2005.India's R&D:Reaching for 1997.Antileuk activity L.307:1415-1417 promoaplysiatoxin 38. Ba P 2 research:A growing gap from Lyngbya.Sci.196:538-540 519
