An amiloride derivative is active against the F₁F_o-ATP synthase and cytochrome bd oxidase of Mycobacterium tuberculosis.

ABSTRACT: Increasing antimicrobial resistance compels the search for next-generation inhibitors with differing or multiple molecular targets. In this regard, energy conservation in Mycobacterium tuberculosis has been clinically validated as a promising new drug target for combatting drug-resistant strains of M. tuberculosis. Here, we show that HM2-16F, a 6-substituted derivative of the FDA-approved drug amiloride, is an anti-tubercular inhibitor with bactericidal properties comparable to the FDA-approved drug bedaquiline (BDQ; Sirturo^®) and inhibits the growth of bedaquiline-resistant mutants. We show that HM2-16F weakly inhibits the F₁F_o-ATP synthase, depletes ATP, and affects the entry of acetyl-CoA into the Krebs cycle. HM2-16F synergizes with the cytochrome bcc-a

SUBMITTER: Hards K 

PROVIDER: S-EPMC8873251 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature