Benzotriazole derivatives as alternate <i>O-</i>acetylserine sulfhydrylase substrates to impair cysteine biosynthesis in gram-negative bacteria.

ABSTRACT: Cysteine biosynthetic pathway, unique to bacteria and absent in the human host, represents a relevant reservoir of potential antimicrobial targets. Cysteine, in fact, is involved in redox homeostasis and is prone to the production of reactive oxygen species, and altering its metabolic equilibrium provokes severe consequences on bacterial fitness and antibiotic response. Here, we developed a library of benzotriazole-derived compounds targeting O-acetylserine sulfhydrylase (OASS)-the enzyme responsible for cysteine synthesis in most pathogenic bacteria-which act as alternate OASS substrates that can impair cysteine production. The library was tested on three clinically relevant gram-negative species, and the three most promising candidates, upon the validation of their mechanism of ac

SUBMITTER: Bova S 

PROVIDER: S-EPMC12637403 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature