Bicyclic Boronates as Potent Inhibitors of AmpC, the Class C β-Lactamase from <i>Escherichia coli</i>.

ABSTRACT: Resistance to β-lactam antibacterials, importantly via production of β-lactamases, threatens their widespread use. Bicyclic boronates show promise as clinically useful, dual-action inhibitors of both serine- (SBL) and metallo- (MBL) β-lactamases. In combination with cefepime, the bicyclic boronate taniborbactam is in phase 3 clinical trials for treatment of complicated urinary tract infections. We report kinetic and crystallographic studies on the inhibition of AmpC, the class C β‑lactamase from Escherichia coli, by bicyclic boronates, including taniborbactam, with different C-3 side chains. The combined studies reveal that an acylamino side chain is not essential for potent AmpC inhibition by active site binding bicyclic boronates. The tricyclic form of taniborbactam was observed b

SUBMITTER: Lang PA 

PROVIDER: S-EPMC7356297 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature