Identification of 2-Aryl-Quinolone Inhibitors of Cytochrome <i>bd</i> and Chemical Validation of Combination Strategies for Respiratory Inhibitors against <i>Mycobacterium tuberculosis</i>.

ABSTRACT: Mycobacterium tuberculosis cytochrome bd quinol oxidase (cyt bd), the alternative terminal oxidase of the respiratory chain, has been identified as playing a key role during chronic infection and presents a putative target for the development of novel antitubercular agents. Here, we report confirmation of successful heterologous expression of M. tuberculosis cytochrome bd. The heterologous M. tuberculosis cytochrome bd expression system was used to identify a chemical series of inhibitors based on the 2-aryl-quinolone pharmacophore. Cytochrome bd inhibitors displayed modest efficacy in M. tuberculosis growth suppression assays together with a bacteriostatic phenotype in time-kill curve assays. Significantly, however, inhibitor

SUBMITTER: Jeffreys LN 

PROVIDER: S-EPMC9926492 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature