Development of Mycobacterium tuberculosis Enoyl Acyl Reductase (InhA) Inhibitors: A Mini-Review

Abstract

This review article delves into the critical role of Enoyl acyl carrier protein reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors. Noteworthy findings highlight thiadiazole and triazole derivatives, demonstrating promising IC50 values within the nanomolar concentration range. The review offers comprehensive insights into InhA's structure, structure-activity relationships, and a detailed overview of distinct scaffolds as effective inhibitors of InhA.

Keywords: InhA inhibitors; Mycobacterium tuberculosis; antitubercular agents; enoyl acyl carrier protein reductase; first-line drug regimens; tuberculosis..