Benzothiazinone analogs as Anti-Mycobacterium tuberculosis DprE1 irreversible inhibitors: Covalent docking, validation, and molecular dynamics simulations.

ABSTRACT: Mycobacterium tuberculosis is a lethal human pathogen, with the key flavoenzyme for catalyzing bacterial cell-wall biosynthesis, decaprenylphosphoryl-D-ribose oxidase (DprE1), considered an Achilles heal for tuberculosis (TB) progression. Inhibition of DprE1 blocks cell wall biosynthesis and is a highly promising antitubercular target. Macozinone (PBTZ169, a benzothiazinone (BTZ) derivative) is an irreversible DprE1 inhibitor that has attracted considerable attention because it exhibits an additive activity when combined with other anti-TB drugs. Herein, 754 BTZ analogs were assembled in a virtual library and evaluated against the DprE1 target using a covalent docking approach. After validation of the employed covalent docking approach, BTZ analogs were screened. Analogs with a docking sco

SUBMITTER: Ibrahim MAA 

PROVIDER: S-EPMC11588222 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature