Indole-containing inhibitors with improved efficacy targeting the gyrase of <i>Mycobacterium tuberculosis</i>.

ABSTRACT: Tuberculosis is a major cause of mortality worldwide, with drug-resistant strains complicating its treatment. We report the discovery of small-molecule inhibitors targeting the gyrase of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. Gyrase, a type II topoisomerase, consists of two subunits: GyrA, which breaks and rejoins DNA, and GyrB, which contains the ATPase domain responsible for ATP binding and hydrolysis. An indole scaffold identified by nuclear magnetic resonance fragment screening was grown into drug-sized candidates through computational optimization, chemical synthesis and functional selection. Several indole-containing gyrase inhibitors were found to be specific for the GyrB subunit of M. tuberculosis. Structural studies using double elect

SUBMITTER: Bhattarai S 

PROVIDER: S-EPMC12429953 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature