Design, Biological Evaluation, and Computer-Aided Analysis of Dihydrothiazepines as Selective Antichlamydial Agents.

ABSTRACT: Chlamydia trachomatis (CT) causes the most prevalent sexually transmitted bacterial disease in the United States. The lack of drug selectivity is one of the main challenges of the current antichlamydial pharmacotherapy. The metabolic needs of CT are controlled, among others, by cylindrical proteases and their chaperones (e.g., ClpX). It has been shown that dihydrothiazepines can disrupt CT-ClpXP. Based on this precedent, we synthesized a dihydrothiazepine library and characterized its antichlamydial activity using a modified semi-high-throughput screening assay. Then, we demonstrated their ability to inhibit ClpX ATPase activity in vitro, supporting ClpX as a target. Further, our lead compound displayed a promising selectivity profile against CT, acceptable cytotoxicit

SUBMITTER: de Campos LJ 

PROVIDER: S-EPMC10056257 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature