Marine natural products as anticancer drugs.

The chemical and biological diversity of the marine environment is immeasurable and therefore is an extraordinary resource for the discovery of new anticancer drugs. Recent technological and methodologic advances in structure elucidation, organic synthesis, and biological assay have resulted in the isolation and clinical evaluation of various novel anticancer agents. These compounds range in structural class from simple linear peptides, such as dolastatin 10, to complex macrocyclic polyethers, such as halichondrin B; equally as diverse are the molecular modes of action by which these molecules impart their biological activity. This review highlights several marine natural products and their synthetic derivatives that are currently undergoing clinical evaluation as anticancer drugs.

[1]  R. G. Hughes,et al.  Structure−Activity Relationships of the Didemnins1,2 , 1996 .

[2]  O. McManus,et al.  Peptides isolated from the venom of Conus geographus block neuromuscular transmission , 1981, Neuroscience Letters.

[3]  M. Broggini,et al.  Effect of Aplidin in acute lymphoblastic leukaemia cells , 2003, British Journal of Cancer.

[4]  Richard E. Moore,et al.  Palytoxin: A New Marine Toxin from a Coelenterate , 1971, Science.

[5]  R. Cerny,et al.  Isolation and Structure of the Cytostatic Linear Depsipeptide Dolastatin 15 , 1989 .

[6]  Arthur J. L. Cooper,et al.  Total synthesis of halichondrins: Enantioselective construction of a homochiral pentacyclic C1-C15 intermediate from d-ribose , 1990 .

[7]  S. Schreiber,et al.  GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha. , 1994, The Journal of biological chemistry.

[8]  A. Lawen,et al.  Rapamycin inhibits didemnin B‐induced apoptosis in human HL‐60 cells: Evidence for the possible involvement of FK506‐binding protein 25 , 1999, Immunology and cell biology.

[9]  M. Joullié,et al.  Natural products as probes of cell biology: 20 years of didemnin research , 2002, Medicinal research reviews.

[10]  C. Salomon,et al.  Localization studies of ioactive cyclic peptides in the ascidian Lissoclinum patella. , 2002, Journal of natural products.

[11]  J. Schellens,et al.  Yondelis (trabectedin, ET-743): the development of an anticancer agent of marine origin. , 2003, Anti-cancer drugs.

[12]  David J Newman,et al.  Natural products as sources of new drugs over the period 1981-2002. , 2003, Journal of natural products.

[13]  F. Sánchez-Jiménez,et al.  Antiproliferative effect of dehydrodidemnin B (DDB), a depsipeptide isolated from Mediterranean tunicates. , 1996, Cancer letters.

[14]  R. G. Hughes,et al.  Structure--activity relationships of the didemnins. , 1996, Journal of medicinal chemistry.

[15]  D. V. Von Hoff,et al.  Phase I and pharmacokinetic study of the water-soluble dolastatin 15 analog LU103793 in patients with advanced solid malignancies. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  J. Sloan,et al.  A Phase II Study of the Dolastatin 15 Analogue LU 103793 in the Treatment of Advanced Non–Small-Cell Lung Cancer , 2003, American journal of clinical oncology.

[17]  T. Barlozzari,et al.  LU103793 (NSC D-669356): a synthetic peptide that interacts with microtubules and inhibits mitosis. , 1995, Cancer research.

[18]  M. Broggini,et al.  Aplidine, a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4 , 2003, Leukemia.

[19]  S. Sudek,et al.  Genetic evidence supports secondary metabolic diversity in Prochloron spp., the cyanobacterial symbiont of a tropical ascidian. , 2004, Journal of natural products.

[20]  F. Schmitz,et al.  Brominated Tyrosine Metabolites from an Unidentified Sponge. , 1988 .

[21]  M. K. Harper,et al.  Symbiotic Bacteria in Sponges: Sources of Bioactive Substances , 2000 .

[22]  V. Paul,et al.  Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. , 2001, Journal of natural products.

[23]  Ian Paterson,et al.  A quantitative evaluation of the effects of inhibitors of tubulin assembly on polymerization induced by discodermolide, epothilone B, and paclitaxel , 2004, Cancer Chemotherapy and Pharmacology.

[24]  Zhao‐Kui Wan,et al.  Synthetic studies on the marine natural product halichondrins , 2003 .

[25]  D. Williams,et al.  Why are secondary metabolites (natural products) biosynthesized? , 1989, Journal of natural products.

[26]  S. O’Day,et al.  Phase II study of synthadotin (SYN-D; ILX651) administered daily for 5 consecutive days once every 3 weeks (qdx5q3w) in patients (Pts) with inoperable locally advanced or metastatic melanoma , 2004 .

[27]  M. Garson,et al.  Cellular origin of chlorinated diketopiperazines in the dictyoceratid sponge Dysidea herbacea (Keller) , 1998, Cell and Tissue Research.

[28]  A. Kraft,et al.  Phase II study of dolastatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[29]  Melvin J. Yu,et al.  Structure-activity relationships of halichondrin B analogues: modifications at C.30-C.38. , 2000, Bioorganic & medicinal chemistry letters.

[30]  J. Jung,et al.  Psammaplin A, a natural phenolic compound, has inhibitory effect on human topoisomerase II and is cytotoxic to cancer cells. , 1999, Anticancer research.

[31]  L. Hurley,et al.  Ecteinascidin 743: a minor groove alkylator that bends DNA toward the major groove. , 1999, Journal of medicinal chemistry.

[32]  M. Hidalgo,et al.  Progress in the development and acquisition of anticancer agents from marine sources. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[33]  E. Hamel,et al.  Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. , 1990, The Journal of biological chemistry.

[34]  N. Lawrence,et al.  Tubulin as a Target for Anticancer Drugs: Agents which Interact with the Mitotic Spindle , 1998 .

[35]  S. Remiszewski The discovery of NVP-LAQ824: from concept to clinic. , 2003, Current medicinal chemistry.

[36]  J. Sloan,et al.  Phase I trial of dolastatin-10 (NSC 376128) in patients with advanced solid tumors. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[37]  N. Saijo,et al.  Antitumor activity of TZT‐1027 (Soblidotin) against vascular endothelial growth factor‐secreting human lung cancer in vivo , 2003, Cancer science.

[38]  A. Ravaud,et al.  Phase II study of LU 103793 (dolastatin analogue) in patients with metastatic breast cancer. , 2003, European journal of cancer.

[39]  S. Lentz,et al.  A phase II trial of dolastatin-10 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. , 2003, Gynecologic oncology.

[40]  W. Gerwick,et al.  Barbamide, a chlorinated metabolite with molluscicidal activity from the Caribbean cyanobacterium Lyngbya majuscula. , 1996, Journal of natural products.

[41]  S. O’Day,et al.  Phase II study of synthadotin (SYN-D; ILX651) administered daily for 5 consecutive days once every 3 weeks (qdx5q3w) in patients (Pts) with inoperable locally advanced or metastatic melanoma. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  T. Mikami,et al.  Synthesis and antitumor activity of novel dolastatin 10 analogs. , 1995, Chemical & pharmaceutical bulletin.

[43]  Christian P. Ridley,et al.  Approaches to identify, clone, and express symbiont bioactive metabolite genes. , 2004, Natural product reports.

[44]  G. Cragg,et al.  National Cooperative Drug Discovery Groups (NCDDGs): A Successful Model for Public Private Partnerships in Cancer Drug Discovery , 2003 .

[45]  T. Mikami,et al.  Antitumor Activity of TZT‐1027, a Novel Doiastatin 10 Derivative , 1997, Japanese journal of cancer research : Gann.

[46]  Paul A. Keifer,et al.  Ecteinascidins 729, 743, 745, 759A, 759B, and 770: potent antitumor agents from the Caribbean tunicate Ecteinascidia turbinata , 1990 .

[47]  Frank Koehn,et al.  Antitumor tetrahydroisoquinoline alkaloids from the colonial ascidian Ecteinascidia turbinata , 1990 .

[48]  Jiro Tanaka,et al.  NORHALICHONDRIN A: AN ANTITUMOR POLYETHER MACROLIDE FROM A MARINE SPONGE , 1985 .

[49]  K. Rinehart,et al.  New Marine Derived Anticancer Therapeutics ─ A Journey from the Sea to Clinical Trials , 2004, Marine Drugs.

[50]  K. Rinehart,et al.  Compounds produced from potential tunicate-blue-green algal symbiosis: A review , 1996, Journal of Industrial Microbiology.

[51]  R. Firn,et al.  Natural Products — A Simple Model to Explain Chemical Diversity , 2003 .

[52]  S. Kuentzel,et al.  Biochemical and cellular effects of didemnins A and B. , 1984, Cancer research.

[53]  O. White,et al.  Environmental Genome Shotgun Sequencing of the Sargasso Sea , 2004, Science.

[54]  P. Scheuer,et al.  Two bromotyrosine-cysteine derived metabolites from a sponge , 1987 .

[55]  J. Schellens,et al.  Pharmaceutical development of anticancer agents derived from marine sources , 2000, Anti-cancer drugs.

[56]  Josef Korinek,et al.  Proceedings of the American Society of Clinical Oncology , 1982 .

[57]  G. Ruggieri Drugs from the sea. , 1976, Science.

[58]  Melvin J. Yu,et al.  In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. , 2001, Cancer research.

[59]  D. Faulkner,et al.  Cyanobacterial symbiont biosynthesis of chlorinated metabolites fromDysidea herbacea (Porifera) , 1993, Experientia.

[60]  P. Crews,et al.  Phenolic constituents of Psammaplysilla , 1987 .

[61]  David J Newman,et al.  Marine natural products and related compounds in clinical and advanced preclinical trials. , 2004, Journal of natural products.

[62]  W. Gerwick,et al.  Nitrogen-containing metabolites from marine cyanobacteria. , 2001, The Alkaloids. Chemistry and biology.

[63]  J. Wanders,et al.  Activity of the dolastatin analogue, LU103793, in malignant melanoma. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[64]  E. Hamel,et al.  Dolastatin 10, a powerful cytostatic peptide derived from a marine animal. Inhibition of tubulin polymerization mediated through the vinca alkaloid binding domain. , 1990, Biochemical pharmacology.

[65]  E. Hamel,et al.  Dolastatin 15 binds in the vinca domain of tubulin as demonstrated by Hummel-Dreyer chromatography. , 2003, European journal of biochemistry.

[66]  Kenneth B. Tomer,et al.  The isolation and structure of a remarkable marine animal antineoplastic constituent: dolastatin 10 , 1987 .

[67]  H. Kwon,et al.  Psammaplin A, a marine natural product, inhibits aminopeptidase N and suppresses angiogenesis in vitro. , 2004, Cancer letters.

[68]  T. Natsume,et al.  Association of p53 gene mutations with sensitivity to TZT‐1027 in patients with clinical lung and renal carcinoma , 2001, Cancer.

[69]  P. Saunders,et al.  Venom of the lionfish Pterois volitans. , 1959, The American journal of physiology.

[70]  K D Paull,et al.  Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. , 1991, The Journal of biological chemistry.

[71]  G. Harrigan,et al.  Symplostatin 1: A dolastatin 10 analogue from the marine cyanobacterium Symploca hydnoides. , 1998, Journal of natural products.

[72]  K. Bair,et al.  Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. , 2003, The Journal of organic chemistry.