Drug Discovery and Development

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Presentation transcript:

Drug Discovery and Development Hits Leads Candidate optimization

PHILIPPINE PHARMASEAS DRUG DISCOVERY PROGRAM Marine Drug Discovery of Anti-Pain Agents from Turrid Snails Anti-Infective Agents from Sponge – Associated Microorganisms

Philippine Mollusk Symbiont International Biodiversity Group (PMS-ICBG) Diverse drug lead compounds from bacterial symbionts in tropical marine mollusks A research collaboration between University of the Philippines Diliman, Oregon Health and Science University, University of Utah, Academy of Natural Sciences of Philadelphia and Ocean Genome Legacy Foundation, USA.

Drug Discovery Pipeline 1 2 Collection and isolation of microorganisms High throughput bioactivity screening 5 3 Novel bioactive compounds 4 Chemical extraction/ Dereplication at compound level Identification of isolates/ Dereplication at producer level

Isolation of Microorganisms 2,737 Marine micoorganisms in collection Field collection of marine sponges, gastropods From database as of April 2012 Isolation of morphologically distinct colony Database and archiving of pure isolates

Bioactivity Screening 169 Antimicrobial Activity Pseudomonas aeruginosa (PA) Klebsiella pneumoniae (KP) Staphylococcus aureus (SA) Methicilin-resistant S. aureus (MRSA) Biofilm-forming S. epidermidis Mammalian Cell Cytotoxicity Antiviral Activity Antifungal Activity Candida albicans (CA) Ampothericin-resistant C. albicans Neuroactivity Dorsal root ganglion assay DRG Antimicrobial priority isolates 78 Cytotoxic priority isolates Neuroactive priority isolates 11 4,872 Yields from assay events

Strategy for Finding High Value Compounds: Purifying compounds from Sponge MMO HPLC Conditions: Shimadzu Prominence HPLC 1 Injected: 50 μL Flow rate: 3.0mL/min Solvent system:Binary gradient, Column: Phenomenex Luna C18 5-100 MeOH in 45 mins 250x10mm, 5μm (semi prep) 100% MeOH Diaion Fraction 6 7 1 2 3 4 5 8 9

Chemical Dereplication UV absorbance spectra Compound matches Hi-res mass spectra + fragmention data AntiMarin* Database + bioactivity and Isolate identity data NMR data (H-H COSY) AntiMarin – is a combined database containing 55,000 reported terrestial and marine natural products Recent tool

Materials Science Materials Bioactive compounds and analogues Nano materials Immuno- liposomes Ionic liquids Hybrid nano- composites Nano composites

Magnetic Resonance Imaging Radiologic pharmaceuticals Polymeric Gd(III)-based macromolecular MRI contrast agents Ln(III)-labelled secondary metabolite peptides as novel molecular imaging tools of pain receptors Ln(III) complexes as spectroscopic labels for targeted diagnostic molecular imaging

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