Tadeusz (‘Ted’) Molinski, PhD Natural Product Drug Design Overview Therapeutic Areas of Interest Natural Products – sources of drug leads Isolation-structure.

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