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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 (PMSICBG) 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. 1 Drug Discovery Pipeline 2 Collection and isolation of microorganisms 5 Novel bioactive compounds High throughput bioactivity screening 4 Chemical extraction/ Dereplication at compound level 3 Identification of isolates/ Dereplication at producer Isolation of Microorganisms 2,737 Marine micoorganisms in collection Field collection of marine sponges, gastropods Isolation of morphologically distinct colony From database as of April 2012 Database and archiving of pure isolates Bioactivity Screening 169 78 Antimicrobial priority isolates Cytotoxic priority isolates Neuroactive priority isolates 11 Yields from 4,872 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 assay events Strategy for Finding High Value Compounds: Purifying compounds from Sponge MMO HPLC Conditions: Shimadzu Prominence HPLC 1 Flow rate: 3.0mL/min Column: Phenomenex Luna C18 250x10mm, 5μm (semi prep) 100% MeOH Diaion Fraction 1 2 3 6 7 4 5 8 9 Injected: 50 μL Solvent system:Binary gradient, 5-100 MeOH in 45 mins Chemical Dereplication UV absorbance spectra Hi-res mass spectra + fragmention data Compound matches + bioactivity and Isolate identity data NMR data (H-H COSY) Recent tool AntiMarin * Database AntiMarin – is a combined database containing 55,000 reported terrestial and marine natural products Materials Science Bioactive compounds and analogues Nano composites Nano materials Materials Hybrid nanocomposites Immunoliposomes Ionic liquids Magnetic Resonance Imaging Polymeric Gd(III)-based macromolecular MRI contrast agents Radiologic pharmaceuticals Ln(III) complexes as spectroscopic labels for targeted diagnostic molecular imaging Ln(III)-labelled secondary metabolite peptides as novel molecular imaging tools of pain receptors Reach us at . . . www.science.upd.edu.ph [email protected] UP Diliman NMR FACILITY Service Form USER INFORMATION SAMPLE INFORMATION EXPERIMENTAL INFORMATION CONDITION/S OF USE I understand and agree to the following: a. That I will be billed according to the half-hourly usage of the NMR plus consumables, if any, based on current schedule of fees. b. Samples submitted will be disposed of after one (1) month of processing if not claimed. c. Data files of processed samples will be disposed of after one (1) month of processing. d. A minimum basic half-hour rate or 50% downpayment, whichever is higher, must be made upon submission of sample. Additional 25% administrative charges will be applied to the total fees. Please pay at the UP Cashier. e. The basic rate includes sample preparation. f. Processing includes e-mail of FID file. g. All experiments that will require more than 30-minute run time will be run during the night queue with a 50% discounted rate on a 2-hr block schedule. h. Day queue is from 8 AM to 5 PM and night queue is from 5 PM to 8 AM. ____________________________________________ Name and Signature of Project Leader/Researcher/Thesis Adviser NMR User Fees Half-hour rate UP certified UP System Other academic institutions Government Industry/Private Consumables: Solvent NMR tubes Processing PhP 400 PhP 550 PhP750 PhP 1,000 PhP 1,500 5 mm NMR tube (500 MHz, 7' long) = PhP 1,675/ NMR tube 3 mm NMR tube (500 MHz, 7' long) = PhP 1,584/NMR tube (for use in inverse detection probe) 5 mm NMR tube (400 MHz, 8' long) = PhP 1,488/tube CDCl3 = PhP 68.5/ml CD3OD = PhP 1,265/ ampoule D2O = PhP 1,886/ ampoule CD3CN = PhP 8,604/ ampoule DMSO-d6 = PhP 2,873/ ampoule Pyridine-d6 Acetone-d6 PhP 200 for e-mail and print-out of full and expanded spectrum with integration and chemical shifts of peaks indicated. NMR Facility Core Group Administration: Dr. Armando Somintac (NIP) and Dr. Neil Andrew Bascos (NIMBB) Promotion and advertisements: Dr. Evangeline C. Amor (IC) and Dr. Christine C. Hernandez (IC) Training and licensing: Dr. Florecita de Guzman (IC), Dr. Portia Mahal G. Sabido (IC), Dr. Aaron Villaraza (IC), Dr. Nemesio E. Montano (MSI) Maintenance: Mr. Miguel Azcuna (MSI) and Ms. Arlene Bartolome (IC) Housekeeping: Dr. Irene M. Villaseñor (IC) Finance: Dr. Irene M. Villaseñor (IC) Business: Dr. Gisela P. Concepcion (MSI)