Drug Discovery from Marine Sources

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Drug Discovery from Marine Sources

• Prof. Dr. Basvaraj K. Nanjwade M. Pharm., Ph. D
• Department of Pharmaceutics
• KLE University College of Pharmacy
• BELGAUM-590010
• Karnataka, INDIA

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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.

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Drug Discovery Process and Productivity
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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

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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.

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Marine Organisms
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Marine Organisms for Drug Discovery

• Life has originated from the oceans that cover
  over 70 of the earths 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.

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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.

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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).

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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

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Prospects for Success
Harbor Bracnch Operates the Johnson-Sea-
Link class subs Depth capability 3000 ft
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Prospects for Success
An Excellent View
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A Variety of Manipulator Tools
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Unique Work Platforms
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How do we choose dive sites?
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600800m
Resolution 20-50m
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Sensors
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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.

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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.

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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.

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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

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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

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Drug Discovery and Development
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Prospects for Success
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Marine Drug Discovery and Development
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Marine Biodiscovery Centre
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Sources of Chemical Diversity
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Generating Chemical Diversity
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Uses of Chemical Diversity
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Screening

• Purified extract library
• Pure compund library
• Structurally defined pure compound library

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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

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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)

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Prospects for Success
Process of Marine Drug Discovery

• Collection
• Biological Screening
• Natural Products Chemistry
• Secondary Testing/Pharmacology
• Production of material for clinical evaluation
• Clinical investigation

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Prospects for Success
Marine Drug Discovery

• 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

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Prospects for Success
Permits for Collections

• 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

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Prospects for Success
Collection Methods

• Wading
• Scuba
• Trawling
• Submersibles

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Prospects for Success
Collection Strategies

• Biological Diversity Chemical Diversity

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Prospects for Success
Screening Approach
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Prospects for Success
Finding Drug to Treat

• Cancer
• - Pancreatic Cancer
• - Multidrug resistant cancers
• - Cancer Specific Agents (NCDDG)
• Infectious Disease
• - Drug resistant staphylococcus aureus
• - Anti-malarial-collaborative UCF, WRAIR
• Neurodegenerative Disease-collaborative
• - Alzhemers
• - Neuroprotection (Stroke)
• Inflammation-collaborative

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Prospects for Success
Extracts are Complex Mixtures of Marine
Products
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Prospects for Success
Natural Products Chemistry

• The Traditional Way

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Prospects for Success
Purification
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Anti-tumor agents from marine sources
currently licensed for development
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Anti-tumor agents from marine sources
currently licensed for development
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Anti-tumor agents from marine sources
currently licensed for development
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Commercially available marine bioproducts
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Commercially available marine bioproducts
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THANK YOUE-mail bknanjwade_at_yahoo.co.inCell
No 0091 9742431000