Design, Synthesis, and Biological Evaluation of Mono- and Diamino-Substituted Squaramide Derivatives as Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthase.

ABSTRACT: Amides of squaric acid are new drug candidates with activity against mycobacteria. Like the approved drug bedaquiline, these compounds achieve efficacy by inhibiting mycobacterial ATP synthase. However, squaramides have a different binding site than bedaquiline and possess the potential to inhibit bedaquiline-resistant strains. We developed an optimized synthesis for monoamino-substituted squaric acid analogues. Guided by an atomic model of a squaramide compound bound to its target, we synthesized 31 new monoamino/diamino-substituted squaric acid derivates. The efficacy of these compounds was determined in whole-cell assays against Mycobacterium tuberculosis and Mycobacterium avium. The molecular target was confirmed with measurement of inhibition of Mycobacterium smegmati

SUBMITTER: Palme PR 

PROVIDER: S-EPMC12703743 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature