PART I: SYNTHESIS AND BIOLOGICAL EVALUATION OF EGCG ANALOGUES AS FATTY ACID SYNTHASE (FASN) I INHIBITORS FOR ANTICANCER THERAPY PART II: SYNTHESIS AND BIOLOGICAL EVALUATION OF 2-AMIDO AND 2-METHYLAMINO SUBSTITUTED BENZO[B]HETEROAROMATICS FOR ANTI-TUBERCULOSIS THERAPY

Abstract

This dissertation comprises two parts. Part I of this thesis involves the development of small molecules to inhibit fatty acid synthase (FASN) as a strategy to kill non-small cell lung cancer (NSCLC) cells. FASN I inhibitors were designed based on (-)-epigallocatechin gallate (EGCG), a known FASN I inhibitor. Through FASN activity assays, western blots and lipid rescue assays, the compounds were shown to induce their cytotoxic effects through FASN I inhibition. In Part II, a series of small molecules were investigated for their effects against Mycobacterium tuberculosis (M. tb). The molecules were modified based on indole-2-carboxamides, a known, potent class of Mycobacterial membrane protein Large 3 (MmpL3) inhibitors, with an intention to create potent anti-tuberculosis compounds with improved solubilities. Amide to amine replacements were able to yield compounds with good potencies against mycobacteria and good aqueous solubilities.