High throughput screening identifies potential inhibitors targeting trimethoprim resistant DfrA1 protein in Klebsiella pneumoniae and Escherichia coli.

ABSTRACT: The DfrA1 protein provides trimethoprim resistance in bacteria, especially Klebsiella pneumoniae and Escherichia coli, by modifying dihydrofolate reductase, which reduces the binding efficacy of the antibiotic. This study identified inhibitors of the trimethoprim-resistant DfrA1 protein through high-throughput computational screening and optimization of 3,601 newly synthesized chemical compounds from the ChemDiv database, aiming to discover potential drug candidates targeting DfrA1 in K. pneumoniae and E. coli. Through this approach, we identified six promising DCs, labeled DC1 to DC6, as potential inhibitors of DfrA1. Each DC showed a strong ability to bind effectively to the DfrA1 protein and formed favorable chemical interactions at the binding sites. These interactions were comparable

SUBMITTER: Hasnat S 

PROVIDER: S-EPMC11871338 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature