Genetic and Cheminformatic Characterization of <i>Mycobacterium tuberculosis</i> Inhibitors Discovered in the Molecular Libraries Small Molecule Repository.

ABSTRACT: High-throughput screening (HTS) of small molecules is a starting point for many drug development pipelines, including tuberculosis. These screens often result in multiple hits whose mechanisms of action remain unknown. From our initial HTS of the Molecular Libraries Small Molecule Repository (MLSMR), we cherry-picked 935 compounds that inhibited the growth of Mycobacterium tuberculosis and set out to provide an early assessment of their antimycobacterial properties and mechanism of action. To characterize the MLSMR Mtb growth inhibitors, a combination of cheminformatics and targeted mutant screening against mutants in katG, hadAB, and a mixed pool of mmpL3 mutants was used to characterize the hits. As a validation of this approach, we identified 101 isoniazid an

SUBMITTER: Eke IE 

PROVIDER: S-EPMC11997997 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature