Drug Discovery from Marine Sources

1. Drug Discovery from Marine Sources Prof. Dr. Basvaraj K. NanjwadeM. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM-590010 Karnataka, INDIA Poona College of Pharmacy, BVDU, Pune.

2. INTRODUCTION • Substances produced by living organisms found in nature have played a critical role in the development of drugs for life-threatening conditions. • Number of recent breakthroughs have resulted in the development and approval of anticancer drugs derived from marine sources such as coral and sponges. Poona College of Pharmacy, BVDU, Pune.

3. Drug Discovery Process and Productivity Poona College of Pharmacy, BVDU, Pune.

4. Discovery Process and Productivity • The discovery process begins with isolation of unique microbes and generation of chemical extracts of biologically active molecules produced by the microbes. • Information on the microorganisms, their sources, culture and extraction conditions, novel chemistries and biological activities have been developed that allow for a concentrated effort on the most productive organisms. • Primary targets leads to identification of novel, biologically active discovery leads in the selected therapeutic areas of oncology and infectious diseases Poona College of Pharmacy, BVDU, Pune.

5. Why Marine? • The marine environment provides a broad range of diverse habitats from which novel sources of natural products can be derived. • Studies from around the world have shown that marine organisms produce a diverse array of metabolites with novel chemical structures and potent biological activities as well as other desirable properties. Poona College of Pharmacy, BVDU, Pune.

6. Marine Organisms Poona College of Pharmacy, BVDU, Pune.

7. Marine Organisms for Drug Discovery • Life has originated from the oceans that cover over 70% of the earth’s surface and contain highly ecological, chemical and biological diversity starting from microorganisms to vertebrates. • The source of unique chemical compounds, which hold tremendous pharmaceutical potential. • Sources emphasize on investigation of the marine ecosystem to explore numerous complex and novel chemical entities. • The sources of new leads for treatment of many diseases such as cancer, AIDS, inflammatory conditions, and a large variety of viral, bacterial and fungal diseases. Poona College of Pharmacy, BVDU, Pune.

8. Marine Organisms for Drug Discovery • Majority of the marine natural products have been isolated from • Sponges, • Coelenterates (sea whips, sea fans and soft corals), • Tunicates, • Opisthobranch molluscs (nudibranchs, sea hares, etc.), • Echinoderms (starfish, sea cucumbers, etc.) and • Bryozoans (moss animals) and a wide variety of marine microorganisms in their tissues. Poona College of Pharmacy, BVDU, Pune.

9. Marine Organisms for Drug Discovery • Sponges, the most primitive multicellular invertebrates, considered as a gold mine during the past 50 years, have fascinated scientists for isolation of promising bioactive compounds for human welfare. • Interestingly, cytarabine (Cytostar-U) also known as Ara-C, a compound isolated from the Caribbean sponge Cryptotheca crypta currently being used with other anticancer drugs in the treatment of acute myelocytic leukaemia (AML). Poona College of Pharmacy, BVDU, Pune.

10. New Tools for Drug Discovery • Exploration of new locations, collection of organisms never before sampled, and identification of chemicals with pharmaceutical potential. • New and improved platforms (such as autonomous, remote, and human occupied underwater vehicles) to take us farther and deeper are in development. • Tools and sensors that have been developed both for space exploration and for diagnostic medicine Poona College of Pharmacy, BVDU, Pune.

11. Harbor Bracnch Operates the Johnson-Sea- Link class subs Depth capability: 3000 ft Prospects for Success Poona College of Pharmacy, BVDU, Pune.

12. An Excellent View Prospects for Success Poona College of Pharmacy, BVDU, Pune.

13. A Variety of Manipulator Tools Poona College of Pharmacy, BVDU, Pune.

14. Unique Work Platforms Poona College of Pharmacy, BVDU, Pune.

15. How do we choose dive sites? Poona College of Pharmacy, BVDU, Pune.

16. 600–800m Resolution 20-50m Poona College of Pharmacy, BVDU, Pune.

17. Poona College of Pharmacy, BVDU, Pune.

18. Sensors Poona College of Pharmacy, BVDU, Pune.

19. Marine Biotechnology • There are numerous opportunities to borrow scientific techniques common to one discipline and apply them innovatively to other areas and questions. • Different marine cyanobacteria to help select the most promising species for pharmaceutical drug discovery efforts, and then using a genomics and molecular biological approach to understand how their unique natural products are created at a genetic and biochemical level. Poona College of Pharmacy, BVDU, Pune.

20. Marine Microbial Drug Leads • The genomics revolution has recently provided an orthogonal approach to the discovery of natural product drug leads in which sequenced genomes are “mined” for biosynthetic pathways. • While promising, this emerging technology faces its own challenges. Poona College of Pharmacy, BVDU, Pune.

21. Genomic to Animal Marine • Marine invertebrate animals provide a robust source for the discovery of bioactive small molecules with the potential to treat human diseases. • Metagenomics affords an efficient and inexpensive method to capture this chemical diversity. • Metagenomics is providing renewed insights into what chemical diversity means and how it originates in the ocean. Poona College of Pharmacy, BVDU, Pune.

22. Primary Metabolites • A primary metabolite is a chemical substance which is required for cells to survive and replicate and is therefore required for survival of the organism • Examples are: – Proteins – Carbohydrates – Lipids – Nucleic acids Poona College of Pharmacy, BVDU, Pune.

23. Secondary Metabolites • A secondary metabolite is a chemical compound produced by an organism which is not required for survival of the organism but presumably confers an evolutionary advantage Poona College of Pharmacy, BVDU, Pune.

24. Drug Discovery and Development Poona College of Pharmacy, BVDU, Pune.

25. Prospects for Success Poona College of Pharmacy, BVDU, Pune.

26. Marine Drug Discovery and Development Poona College of Pharmacy, BVDU, Pune.

27. Marine Biodiscovery Centre Poona College of Pharmacy, BVDU, Pune.

28. Sources of Chemical Diversity Poona College of Pharmacy, BVDU, Pune.

29. Generating Chemical Diversity Poona College of Pharmacy, BVDU, Pune.

30. Uses of Chemical Diversity Poona College of Pharmacy, BVDU, Pune.

31. Screening • Purified extract library • Pure compund library • Structurally defined pure compound library Poona College of Pharmacy, BVDU, Pune.

32. Expertise • Structural characterisation of organic compounds and element/isotope-tagged biomolecules • Spectroscopic expertise: • Nuclear magnetic resonance • Liquid chromatography - mass spectrometry • Inductively coupled plasma - mass spectrometry (ICPMS) • Elemental Imaging: laser ablation ICPMS • Gas chromatography - ICPMS Poona College of Pharmacy, BVDU, Pune.

33. Facilities • 600 & 400 MHz Nuclear Magnetic Resonance • High and low resolution LC-MS • High and low resolution ICP-MS • Parallel HPLC - ESMS/ICPMS • Fully equipped microbial culture suite • Separations/chromatography suite (eg SPE, SEC, HPLC) Poona College of Pharmacy, BVDU, Pune.

34. Process of Marine Drug Discovery Prospects for Success • Collection • Biological Screening • Natural Products Chemistry • Secondary Testing/Pharmacology • Production of material for clinical evaluation • Clinical investigation Poona College of Pharmacy, BVDU, Pune.

35. Marine Drug Discovery Prospects for Success • Requires a Multidisciplinary Team • Biologists - Marine Biologist - Cell Biologists; Immunologists, Virologists - Pharmacologists/Biochemists - Molecular Biologists • Chemists - Natural Products Chemists - Spectroscopists - Synthetic/Medicinal Chemists • Business Professionals - Marketing/Technology Transfer/Patent Attorneys Poona College of Pharmacy, BVDU, Pune.

36. Permits for Collections Prospects for Success • Before you collect-Get the right permits • International Convention on Biological Diversity – http://www.biodiv.org/convention/articles.asp • You must have informed consent of host country – Permits may be issued at a local or country level – Work with State Governments for State waters; National marine Fisheries for Federal – Special Permits for Marine Sanctuaries • Often a Memorandum of Understanding is negotiated prior to collection – Participation by Host Nation in Project – Return of Income/Benefit to Host Country – Reporting requirements – Sharing of specimens and information on samples Poona College of Pharmacy, BVDU, Pune.

37. Collection Methods Prospects for Success • Wading • Scuba • Trawling • Submersibles Poona College of Pharmacy, BVDU, Pune.

38. Collection Strategies Prospects for Success • Biological Diversity = Chemical Diversity Poona College of Pharmacy, BVDU, Pune.

39. Screening Approach Prospects for Success Poona College of Pharmacy, BVDU, Pune.

40. Finding Drug to Treat Prospects for Success • Cancer - Pancreatic Cancer - Multidrug resistant cancers - Cancer “Specific” Agents (NCDDG) • Infectious Disease - Drug resistant staphylococcus aureus - Anti-malarial-collaborative UCF, WRAIR • Neurodegenerative Disease-collaborative - Alzhemer’s - Neuroprotection (Stroke) • Inflammation-collaborative Poona College of Pharmacy, BVDU, Pune.

41. Extracts are Complex Mixtures of Marine Products Prospects for Success Poona College of Pharmacy, BVDU, Pune.

42. Natural Products Chemistry Prospects for Success • The Traditional Way Poona College of Pharmacy, BVDU, Pune.

43. Purification Prospects for Success Poona College of Pharmacy, BVDU, Pune.

44. Anti-tumor agents from marine sources currently licensed for development Poona College of Pharmacy, BVDU, Pune.

45. Anti-tumor agents from marine sources currently licensed for development Poona College of Pharmacy, BVDU, Pune.

46. Anti-tumor agents from marine sources currently licensed for development Poona College of Pharmacy, BVDU, Pune.

47. Commercially available marine bioproducts Poona College of Pharmacy, BVDU, Pune.

48. Commercially available marine bioproducts Poona College of Pharmacy, BVDU, Pune.

49. THANK YOUE-mail: bknanjwade@yahoo.co.inCell No: 0091 9742431000 Poona College of Pharmacy, BVDU, Pune.