Discovery of Boronic Acids-Based β-Lactamase Inhibitors Through In Situ Click Chemistry.

ABSTRACT: In this study, we evaluated in situ click chemistry as a platform for discovering boronic acid-based β-lactamase inhibitors (BLIs). Unlike conventional drug discovery approaches requiring multi-step synthesis, protection strategies, and extensive screening, the in situ method can allow for the generation and identification of potent β-lactamase inhibitors in a rapid, economic, and efficient way. Using KPC-2 (class A carbapenemase) and AmpC (class C cephalosporinase) as templates, we demonstrated their ability to catalyse azide-alkyne cycloaddition, facilitating the formation of triazole-based β-lactamase inhibitors. Initial screening of various β-lactamases and boronic warheads identified compound 3 (3-azidomethylphenyl boronic acid) as the most effective scaffold for kinetic target

SUBMITTER: Santi N 

PROVIDER: S-EPMC12071365 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature