1. Tadeusz (‘Ted’) Molinski, PhD Natural 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 Ca 2+ ion channels: ‘channelopathies’ S Crypto. grubii : MIC 50 0.85 µM

2. 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

3. 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: IC 50 66 nM* * Collaboration with Drs. Januario Castro & Michael Choi, MCC