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Marine Pharmaceuticals

Slides from an in-class pharmacology presentation at Trent University in Biol-4320H presented in winter of 2011-2012.

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Marine Pharmaceuticals

  1. 1. Marine Pharmaceuticals Drugs from the DeepPresented by: Justin Porter BIOL 4320H Winter 2012
  2. 2. Why look to the Sea?• Biodiversity and evolution of unique defensive compounds• Approx. 11,000 marine compared to 155,000 terrestrial derived drugs• New treatments for MDR• Low toxic side effects
  3. 3. Diving into marine drug development• Properties discovered: •Anti-bacterial •Anti-coagulant •Anti-fungal •Anti-protozoal •Anti-tuberculosis •Anti-viral
  4. 4. Sponges
  5. 5. Sponges• Anti-viral: •Currently on the market •Acyclovir •Ara-A (vidarabine) •Ara-C (cytarabine) •In development •4-methylaaptamine •EC50 = 2.4 µM •Verongiaquinol
  6. 6. Sponges (continued)• Anti-bacterial & Anti-fungal: •Verongiaquinol •MIC = 8 µg/mL •Manzamine A •Broad-spectrum vs Gram-positive •Good vs Gram-negative •Verongiaquinol and Manzamine A are very effective antifungal agents.
  7. 7. Sponges (continued)• Anti-protozoal & Anti-tuberculosis: •Xestoquinone •Anti-malarial polyketide •Pfnek-1 kinase inhibition •IC50 = 1.1 µM to 3 µM •Manzamine Alkaloids •Inhibit M. tuberculosis •IC50 = 0.4 µg/mL to 5.2 µg/mL •6-hydroxymanzamine E is most potent
  8. 8. Marine Bacteria
  9. 9. Marine Fungi
  10. 10. Fungi• Anti-viral & Anti-bacterial: •Halovirs A-E •Linear peptides from Scytidium spp. •Halovir A Inhibits HSV-1 and HSV-2 •EC50 = 280 nM •Corollosporine •Antibacterial metabolite •Isolated from Corollospora maritime
  11. 11. Algae
  12. 12. Algae• Anti-viral: •Most antiviral compounds from marine algae are polysaccharides •Diterpenes from Dictyota spp. •Inhibit HIV-1 reverse transcriptase •Dolabelladienetriol •Terpenoid from Sargassum binderi •Non-competitive inhibitor of HIV-1 RT
  13. 13. Algae (continued)• Anti-inflammatory & Anti-fungal: •Fucoxanthin •Pigment from Myagropsis myagorides •Anti-inflammatory effect rivals the current SAID predinisolone! •Extracts from Odonthalia corymbifera •Potent inhibition of fungal Isocitrate Lysase •IC50 = 23 µg/mL •May be effective against Candida albicans
  14. 14. Fish
  15. 15. FishAnti-bacterial Properties• Innate antimicrobial arsenal of complements, lectins andlysozymes in the mucus and serum• Acidic glycoprotien L-amino acid oxidase (LAO) wasisolated from Rockfish (Sebastes schlegelii) •Specifically catalyzes L-lysine •Induces damage and morphological changes to bacterial cell surface
  16. 16. Fish (continued)Anti-coagulant Properties•Monomeric protein isolated from Yellowfin sole (Limandaaspera) inhibited serine endopeptidase factor XII•Controls platelet aggregation by creating an inactivecomplex
  17. 17. Corals
  18. 18. Corals• Anti-inflammatory: •Pseudopterosin A •Diterpene glycoside from Pseudopterogorgia elisabethae (Caribbean Sea Whip) •Anti-inflammatory effect rivals industry standards •Used in some Estée Lauder cosmetics
  19. 19. Other Marine Organisms
  20. 20. • Many promising compounds in preclinical stages: •TGAP •Anticoagulant polypeptide from Tegillarca granosa (Malaysian cockle) •Inhibits conversion of prothrombin to thrombin
  21. 21. Future of Marine Pharmaceuticals• Challenges: •Accessibility •Rarity •Endangered or protected species and their products require cumbersome permitting procedures •Large-scale production •Chemical synthesis may be a solution for some •Acyclovir •Cultivation using bioreactors •Combinatorial biosynthesis•There are many more discoveries to be made!
  22. 22. Conclusions
  23. 23. ReferencesAqil, F., M. Zahin, K.A. El Sayed, I. Ahmad, K.Y. Orabi, and J.M. Kijjoa A. and P. Sawangwong. 2004. Drugs and Cosmetics Arif. 2011. Antimicrobial antioxidant, and anitmutagenic from the Sea. Mar. Drugs. 2: 73-82. activities of selected marine natural products and Kitani Y., N. Kikuchi, G. Zhang, S. Ishizaki, K. Shimakura, K. tobacco cembranoids. Drug and Chemical Toxicology, Shiomi and Y. Nagashima. 2008. Antibacterial action of 24(2): 167-179. L-amino acid oxidase from the skin mucus of rockfishBerrue, F., O.P. Thomas, R. Laville, S. Prado, J. Golebiowski, R. Sebastes schlegelii. CBP Part B: Biochemistry and Fernandez, and P. Amade. 2007. The marine sponge Molecular Biology. 149( 2): 394-400. Plakortis zyggompha: a source of original bioactive Larghi, E.L., M.L. Bohn, and T.S. Kaufman. 2009. Aaptamine polyketides. Tetrahedron. 63: 2328-2334. and related products. Their isolation, chemicalDe Souza Pereira H., L.R. Leaso-Ferreira, N. Moussatche, V.L. syntheses, and biological activity. Tetrahedron, 65: Telixeira , D.N. Cavalcanti, L.J. Da Costa and I.C. 4257-4282. Fruulhetti. 2005. Effects of diterpenses isolated from Leary, D., M. Vierros, G. Hamon, S, Arico and C. Monagle. the Brazilian marine alga Dictyota menstrualis on HIV-1 2009. Marine genetic resources: A review of scientific reverse transcriptase. Planta Med. 71(11): 1019-24. and commercial interest. Marine Policy, 33: 183-194.El-Amraoui, B., J.F. Biard, M.J. Uriz, S. Rifai, and A. Fassouane. Lee, J.B. , K. Hayashi, M. Hirata, E. Kuroda, E. Suzuki, Y. Kubo, 2010. Antifungal and antibacterial activity of Porifera and T. Hayashi. 2006. Antiviral sulfated polysaccharide extracts from the Moroccan Atlantic coasts. Journal de from Navicula directa, a diatom collected from deep- Mycologie Médicale. 20: 70-74. seawater in Toyama Bay, Biol. Pharm. Bull. 29: 2135–Imhoff, J.F., A. Labes, and J. Wiese. 2011. Bio-mining the 2139. microbial treasures of the ocean: New natural products. Mayer, A.M.S, A.D. Rodriguez, R.G.S. Berlinck and M.T. Biotechnology Advances. 29: 468-482. Hamann. 2009. Marine pharmacology in 2005-6:Jacquet, S., T. Miki, R. Noble, P. Peduzzi and S. Wilhelm. Marine compounds with anthelmintic, antibacterial, 2010. Viruses in aquatic ecosystems: important anticoagulant, antifungal, anti-inflammatory, advancements of the last 20 years and prospects for the antimalarial, antiprotozoal, antituberculosis an antiviral future in the field of microbial oceanography and activies; affecting the cardiovascular, immune and limnology. Advances in Oceanography and Limnology, nervous systems, and other miscellaneous mechanisms 1(1): 97-141. of action. Biochima et Biophysica Acta, 1790: 283-308.
  24. 24. References (continued)Mayer A.M.S., A.D. Rodriguez, R.G.S. Berlinck and N. Fusetani. Subramanian, S., N.W. Ross and S.L. Mackinnon. 2008. 2011. Marine pharmacology in 2007-8: Marine Comparison of antimicrobial activity in the epidermal compounds with antibacterial, anticoagulant, mucus extracts of fish. CBP Part B: Biochemisty and antifungal, anti-inflammatory, antimalarial, Molecular Biology, 150(1): 85-92 antiprotozoal, antitberculosis and antiviral activities: Villa, F.A. and L. Gerwick. 2010. Marine natural products affecting the immune and nervous system, and other discovery: Leads for treatment of inflammation, cancer, miscellaneous mechanisms of action. Comparative infections, and neurological disorders. Biochemistry and Physiology, Part C. 153: 191-222. Immunopharmacology and Immunotoxicology, 32(2):Pangestuti R. and S. Kim. 2011. Biological activities and 228-237. health benefit effects of natural pigments derived from Vo, T., D. Ngo, Q.V. Ta and S. Kim. 2011. Marine organisms as marine algae. Journal of Functional Foods, 3:255-266. a therapeutic source against herpes simplex virusQi S.H., S. Zhang, L.H. Yang and Qian P.Y. 2008. Antifouling infection. European Journal of Pharmaceutical Science, and antibacterial compounds from the gorgians 44: 11-20. Subergorgia gracillis. Natural Products Research, 22 (2): Wase, N.V. and P.C. Wright. 2008. Systems biology of 154-166 cyanobacterial secondary metabolite production and itsRastogi, R.P. and R.P. Sinha. 2009. Biotechnological and role in drug discovery. Expert Opin. Drug Discov., 3(8): industrial significance of cyanobacterial secondary 903-929. metabolites. Biotechnology Advances, 27: 521-539. Wiliams, P.G. 2008. Planning for chemical gold: marineSperstad S.V., T. Haug, H. Blencke, O.B. Styrvoid, C. Li and K. bacteria as a source of new therapeutics. Trends in Stensvag. 2011. Antimicrobial peptides from marine Biotechnology, 27(1): 45-52. invertebrates: Chanllenges and perspectives in marine Uzair B., Z. Mahmood and S. Tabassum., 2011. Antiviral antimicrobial peptide discovery. Biotechnology activity of natural products extracted from Marine Advances. 29: 519-530. organisms. BioImpacts 1(4): 203-211.Stengel, D.B., S. Connan and Z.A. Popper. 2011. Algal Yasuhara-Bell, J. and Y. Lu. 2010. Marine compounds and chemodiversity and bioactivity: Sources of natural their antiviral activities. Antiviral Research, 66: 231-240 variability and implications for commercial application. Biotechnology Advances, 29: 483-501.
  25. 25. References (continued)Mayer A.M.S., A.D. Rodriguez, R.G.S. Berlinck and N. Fusetani. Subramanian, S., N.W. Ross and S.L. Mackinnon. 2008. 2011. Marine pharmacology in 2007-8: Marine Comparison of antimicrobial activity in the epidermal compounds with antibacterial, anticoagulant, mucus extracts of fish. CBP Part B: Biochemisty and antifungal, anti-inflammatory, antimalarial, Molecular Biology, 150(1): 85-92 antiprotozoal, antitberculosis and antiviral activities: Villa, F.A. and L. Gerwick. 2010. Marine natural products affecting the immune and nervous system, and other discovery: Leads for treatment of inflammation, cancer, miscellaneous mechanisms of action. Comparative infections, and neurological disorders. Biochemistry and Physiology, Part C. 153: 191-222. Immunopharmacology and Immunotoxicology, 32(2):Pangestuti R. and S. Kim. 2011. Biological activities and 228-237. health benefit effects of natural pigments derived from Vo, T., D. Ngo, Q.V. Ta and S. Kim. 2011. Marine organisms as marine algae. Journal of Functional Foods, 3:255-266. a therapeutic source against herpes simplex virusQi S.H., S. Zhang, L.H. Yang and Qian P.Y. 2008. Antifouling infection. European Journal of Pharmaceutical Science, and antibacterial compounds from the gorgians 44: 11-20. Subergorgia gracillis. Natural Products Research, 22 (2): Wase, N.V. and P.C. Wright. 2008. Systems biology of 154-166 cyanobacterial secondary metabolite production and itsRastogi, R.P. and R.P. Sinha. 2009. Biotechnological and role in drug discovery. Expert Opin. Drug Discov., 3(8): industrial significance of cyanobacterial secondary 903-929. metabolites. Biotechnology Advances, 27: 521-539. Wiliams, P.G. 2008. Planning for chemical gold: marineSperstad S.V., T. Haug, H. Blencke, O.B. Styrvoid, C. Li and K. bacteria as a source of new therapeutics. Trends in Stensvag. 2011. Antimicrobial peptides from marine Biotechnology, 27(1): 45-52. invertebrates: Chanllenges and perspectives in marine Uzair B., Z. Mahmood and S. Tabassum., 2011. Antiviral antimicrobial peptide discovery. Biotechnology activity of natural products extracted from Marine Advances. 29: 519-530. organisms. BioImpacts 1(4): 203-211.Stengel, D.B., S. Connan and Z.A. Popper. 2011. Algal Yasuhara-Bell, J. and Y. Lu. 2010. Marine compounds and chemodiversity and bioactivity: Sources of natural their antiviral activities. Antiviral Research, 66: 231-240 variability and implications for commercial application. Biotechnology Advances, 29: 483-501.
  26. 26. QUESTIONS?

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