Boronic Acid Transition State Inhibitors as Potent Inactivators of KPC and CTX-M β-Lactamases: Biochemical and Structural Analyses.

ABSTRACT: Design of novel β-lactamase inhibitors (BLIs) is one of the currently accepted strategies to combat the threat of cephalosporin and carbapenem resistance in Gram-negative bacteria. Boronic acid transition state inhibitors (BATSIs) are competitive, reversible BLIs that offer promise as novel therapeutic agents. In this study, the activities of two α-amido-β-triazolylethaneboronic acid transition state inhibitors (S02030 and MB_076) targeting representative KPC (KPC-2) and CTX-M (CTX-M-96, a CTX-M-15-type extended-spectrum β-lactamase [ESBL]) β-lactamases were evaluated. The 50% inhibitory concentrations (IC₅₀s) for both inhibitors were measured in the nanomolar range (2 to 135 nM). For S02030, the k₂/K for CTX-M-96 (24,0

SUBMITTER: Alsenani TA 

PROVIDER: S-EPMC9872677 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature