tadeusz (‘ted’) molinski, phd natural product drug design overview therapeutic areas of interest...
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Tadeusz (‘Ted’) Molinski, PhDNatural Product Drug Design
Overview
Therapeutic Areas of Interest
• Natural Products – sources of drug leads• Isolation-structure elucidation of marine natural products (MNPs)• Organic synthesis & Structure-Activity Relationships (SAR)• Medicinal Chemistry
• Antifungals to azole-resistant yeast (e.g. Candida spp. emergent pathogens (e.g. Crypto. grubii, & C. gatti)• Cancer – CLL, solid tumors, c-kit, wnt develop. pathways, HDAC inhibitors• Ca2+ ion channels: ‘channelopathies’
S
Crypto. grubii : MIC50 0.85 µM
Core Expertise
Natural Products - Discovery• Collection-archiving of marine invertebrates• Isolation-purification, structure elucidation (SE) of rare MNPs– Nuclear Magnetic Resonance (NMR)– Mass spectrometry (MS), FTIR, circular dichroism (CD)– Integrated techniques: synthesis & spectr. methods• Chemical biology – mechanism/target of action.• Method development and application for SE (NMR, CD)
Organic Synthesis• Medicinal Chemistry – ‘short-order cook’• Total Synthesis of complex MNPs – ’grand banquet’• SAR – refinement of lead compounds
Proposed Collaborations with SSPPS Faculty
MNP – ligand binding targets
• Chemical biology of natural products – ‘pull down’ of cognate receptor/enzymes – proteomics: identification of high-affinity protein targets – target validation
MNP – screening and post-lead • Eukaryotic pathogens – fungal infectious disease (histoplasmosis, coccidiomycoses) – PK, PD, ADME – in vivo animal models, trials
CLL: IC50 66 nM*
* Collaboration with Drs. Januario Castro & Michael Choi, MCC