A renaissance in marine pharmacology: from preclinical curiosity to clinical reality.

Marine pharmacology, the pharmacology of marine natural products, has been for some time more associated with marine natural products chemistry rather than mainstay pharmacology. However, in recent years a renaissance has occurred in this area of research, and has seen the US Food & Drug Administration (FDA) approval in 2004 of Prialt (ziconotide, omega-conotoxin MVIIA) the synthetic equivalent of a conopeptide found in marine snails, used for the management of severe chronic pain. Furthermore Yondelis) (trabectedin, ET-743) an antitumor agent scovered in a marine colonial tunicate, and now produced synthetically, receiving Orphan Drug designation from the European Commission (EC) and FDA for soft tissue sarcomas and ovarian cancer and its registration in 2007 in the EU for the treatment of soft tissue sarcoma. The approval/marketing of so few marine natural products has come after many years of research primarily by the academic community and the sporadic involvement of major pharmaceutical companies. This commentary, through the opinions provided by several leaders in the marine natural products field, will examine the potential reasons and perceptions from both the academic and pharmaceutical communities regarding the development of marine natural products as viable therapeutic entities.

[1]  C. Bailly.  Ready for a comeback of natural products in oncology. , 2009, Biochemical pharmacology.

[2]  A. Arukwe,et al.  Molecular cloning of rainbow trout (Oncorhynchus mykiss) eggshell zona radiata protein complementary DNA: mRNA expression in 17beta-estradiol- and nonylphenol-treated fish. , 2002, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[3]  M. Hamann,et al.  Marine pharmacology in 2001--2002: marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other , 2005, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[4]  Gisbert Schneider,et al.  Scaffold diversity of natural products: inspiration for combinatorial library design. , 2008, Natural product reports.

[5]  D. Hopwood.  Therapeutic treasures from the deep. , 2007, Nature chemical biology.

[6]  M. Hamann,et al.  Marine pharmacology in 1999: compounds with antibacterial, anticoagulant, antifungal, anthelmintic, anti-inflammatory, antiplatelet, antiprotozoal and antiviral activities affecting the cardiovascular, endocrine, immune and nervous systems, and other miscellaneous mechanisms of action. , 2002, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[7]  M. Hamann,et al.  Marine pharmacology in 2003-4: marine compounds with anthelmintic antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous mech , 2007, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[8]  P. Long,et al.  Marine metabolites and metal ion chelation: intact recovery and identification of an iron(II) complex in the extract of the ascidian Eudistoma gilboviride. , 2008, Angewandte Chemie.

[9]  William Fenical,et al.  Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica , 2007, Proceedings of the National Academy of Sciences.

[10]  M. Hamann,et al.  Marine Pharmacology in 2000: Marine Compounds with Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antituberculosis, and Antiviral Activities; Affecting the Cardiovascular, Immune, and Nervous Systems and Other Miscellaneous Mechanisms of Action , 2003, Marine Biotechnology.

[11]  K. Gustafson,et al.  Marine pharmacology in 2005-2006: antitumour and cytotoxic compounds. , 2004, European journal of cancer.

[12]  Robert J. Feeney,et al.  CONTRIBUTIONS TO THE STUDY OF MARINE PRODUCTS. XXXII. THE NUCLEOSIDES OF SPONGES. I.1 , 1951 .

[13]  K. S. Lam,et al.  Discovery and development of the anticancer agent salinosporamide A (NPI-0052). , 2009, Bioorganic & medicinal chemistry.

[14]  D. Faulkner,et al.  Marine pharmacology , 2004, Antonie van Leeuwenhoek.

[15]  William H Gerwick,et al.  Marine natural products as anticancer drugs. , 2005, Molecular cancer therapeutics.

[16]  K. Gustafson,et al.  Marine pharmacology in 2001-2: antitumour and cytotoxic compounds. , 2004, European journal of cancer.

[17]  B. Olivera,et al.  Conus Peptides: Biodiversity-based Discovery and Exogenomics* , 2006, Journal of Biological Chemistry.

[18]  F. Peláez,et al.  Biodiversity, chemical diversity and drug discovery. , 2008, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[19]  H. Gilman,et al.  Notes - Some Aromatic and Heterocyclic Derivatives of Carbazole , 1957 .

[20]  D. Faulkner.  Marine natural products (1999) , 2001 .

[21]  K. Gustafson,et al.  Marine pharmacology in 2000: Antitumor and cytotoxic compounds , 2003, International journal of cancer.

[22]  A. Mayer.  Marine pharmacology in 1999 : compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, anthelmintic, anti-inflammatory, antiplatelet, antiprotozoal and antiviral activities ; affecting the cardiovascular, endocrine, immune, and nervous systems ; and other miscellaneous mechanisms , 2002 .

[23]  William Fenical,et al.  Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. , 2003, Angewandte Chemie.

[24]  W. Bergmann,et al.  Contributions to the Study of Marine Products. XLIII. The Nucleosides of Sponges. V. The Synthesis of Spongosine1 , 1957 .

[25]  S. Kehraus,et al.  Natural Products from Marine Organisms and Their Associated Microbes , 2006, Chembiochem : a European journal of chemical biology.

[26]  W. Gerwick,et al.  Somocystinamide A, a novel cytotoxic disulfide dimer from a Fijian marine cyanobacterial mixed assemblage. , 2002, Organic letters.

[27]  T. Molinski,et al.  Drug development from marine natural products , 2009, Nature Reviews Drug Discovery.

[28]  A. Mayer,et al.  Marine pharmacology in 1999: antitumor and cytotoxic compounds. , 2001, Anticancer research.

[29]  D. Faulkner.  Marine natural products. , 2000, Natural product reports.

[30]  B. Olivera,et al.  Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery. , 2007, Molecular interventions.

[31]  A. Bull,et al.  Marine actinobacteria: new opportunities for natural product search and discovery. , 2007, Trends in microbiology.

[32]  M. Saleem,et al.  Marine Natural Products of Fungal Origin , 2008 .

[33]  Hartmut Laatsch,et al.  Evolving trends in the dereplication of natural product extracts: new methodology for rapid, small-scale investigation of natural product extracts. , 2008, Journal of natural products.

[34]  Lik Tong Tan,et al.  Bioactive natural products from marine cyanobacteria for drug discovery. , 2007, Phytochemistry.

[35]  M. K. Harper,et al.  Marine Natural Product Libraries for High-Throughput Screening and Rapid Drug Discovery , 2008, Journal of natural products.

[36]  A. V. van Oosterom,et al.  Clinical impact of trabectedin (ecteinascidin-743) in advanced/metastatic soft tissue sarcoma. , 2008, Expert opinion on pharmacotherapy.

[37]  K. Gustafson,et al.  Marine pharmacology in 2003-2004: anti-tumour and cytotoxic compounds. , 2006, European journal of cancer.

[38]  M. Hamann,et al.  Marine pharmacology in 2005-6: Marine compounds with anthelmintic, antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of act , 2009, Biochimica et biophysica acta.

[39]  Frank E Koehn,et al.  High impact technologies for natural products screening. , 2008, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[40]  R. Hill,et al.  New drugs from marine microbes: the tide is turning , 2006, Journal of Industrial Microbiology and Biotechnology.

[41]  W. Bergmann,et al.  Contributions to the Study of Marine Products. XL. The Nucleosides of Sponges.1 IV. Spongosine2 , 1956 .

[42]  W. Gerwick,et al.  The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8 , 2008, Proceedings of the National Academy of Sciences.

[43]  U. Klotz.  Ziconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review. , 2006, International journal of clinical pharmacology and therapeutics.

[44]  K. Hinrichs,et al.  Significant contribution of Archaea to extant biomass in marine subsurface sediments , 2008, Nature.

[45]  Marcel Jaspars,et al.  Biomedical research tools from the seabed. , 2007, Current opinion in drug discovery & development.