Dr. Ted Molinski: Natural Products Drug Discovery

Molinski

Tadeusz Molinski, Ph.D.
Professor of Chemistry, Department of Chemistry and Biochemistry
Professor of Pharmacy, Skaggs School of Pharmacy & Pharmaceutical Sciences (SSPPS)
Center for Marine Biotechnology and Biomedicine (CMBB), Scripps Institution of Oceanography
University of California, San Diego

Telephone:
(858) 534-7115
Email:
tmolinski@ucsd.edu

Research Summary: Marine Natural Products

Professor Molinski conducts research on the structural, synthetic and biological chemistry of marine natural products from marine sponges (Porifera), ascidians, and environmental bacteria. This includes chemical investigation and methods development for discovery of exceedingly small amounts of rare natural products ('nano-mole scale') using NMR, circular dichroism (CD) and mass spectrometry (MS), and synthesis of drug-like analogs for important therapeutic areas.

Therapeutic Areas

  • Cancer chemo-therapeutics
  • Antifungal agents
  • Kinase and phosphatase inhibitors
  • Ca2+
  • channel modulators
  • Targeted-enzyme inhibitors for cancer and infectious disease

Academic Achievements

Education: Ph.D. (1985) Australian National University, Canberra; Postdoctoral studies (1985-87) Scripps Institution of Oceanography, UCSD; (1987- 88) University of Utah.

Awards & Honors: Albert Hofmann Centennial Prize – elucidation of structures of natural marine products (2006); Chair of the Gordon Conference in Marine
Natural Products (2004); Editorial advisory boards including Journal of Organic Chemistry, Journal of Natural Products, and Australian Journal of Chemistry.

Leadership Experience: Managed a high-visibility research effort for over 20 years. Consultant for biotech industries. Management and fund raising for national and international symposia on natural products sciences. One of the founding ‘Faculty of 1000’ reviewers in Biology.

Teaching

  • Advanced Organic Chemistry (SPPS 221).
  • Organic Spectroscopy (CHEM258).
  • Introduction to Organic Chemistry (CHEM140B).
  • Research (CHEM199, 299).

Translational Applications to Drug Discovery and Clinical Medicine

  • Discovery of a potent Wnt-inhibitor (with co- investigators at the UCSD Moores Cancer Center).
  • Screening and identification of natural products active against fungal pathogens: Cryptococcus spp., Candida spp., especially Fluconazole- resistant strains.
  • Discovery of pro-apoptotic compounds from screening against cancer cell lines.
  • Discovery of phorboxazoles A and B, potent cytostatic agents against colon tumor cells (HCT- 116).

Selected Recent Publications (from >140 peer reviewed articles)

Gafni et al. (1997). Xestospongins: Potent Membrane Permeable Blockers of the Inositol 1,4,5- Trisphosphate Receptor. Neuron 19:723-733.

Mulder et al. (2009). Synthesis and Structure-activity Relationships of Bengazole A Analogs Bioorg Med Chem Lett 19:2928-2930.

Dalisay et al. (2009). A Tetrachloro Polyketide Hexahydro-1H-isoindolinone, Muironolide A, from the Sponge Phorbas sp. Natural Products at the Nanomole-Scale. J Am Chem Soc 131:7552-7553.

Molinski et al. (2009). Drug Development from Marine Natural Products. Nature Rev Drug Discov 28:69-85.

Potential Collaboration Programs with the Pharmaceutical Industry

  • Expertise in natural products isolation-structure elucidation (NMR, CD, MS), screening and identification of novel biologically active compounds.
  • Synthesis of small-molecule cellular probes. Intellectual Property: 3 patents.