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Publication Abstract from PubMed

Bacterially expressed beta-lactamases are rapidly eroding the clinical utility of the important beta-lactam class of antibacterials, significantly impairing our ability to fight serious bacterial infections. This paper describes a study of oxaborole-derived beta-lactamase inhibitors in which crystal structures and computational modeling aided in the rational design of analogues with improved spectrum of activity against class A, C, and D enzymes. Crystal structures of two of these inhibitors covalently bound to two different serine beta-lactamases, class C Pseudomonas aeruginosa AmpC and class D OXA-10, are described herein. Improved physicochemical properties as well as increased activity against an array of beta-lactamases resulted in substantial restoration of susceptibility to ceftazidime in Escherichia coli and Klebsiella pneumoniae.

4,5-Disubstituted 6-Aryloxy-1,3-dihydrobenzo[c][1,2]oxaboroles Are Broad-Spectrum Serine beta-Lactamase Inhibitors.,McKinney DC, Zhou F, Eyermann CJ, Ferguson AD, Prince DB, Breen J, Giacobbe RA, Lahiri S, Verheijen JC ACS Infect Dis. 2015 Jul 10;1(7):310-6. doi: 10.1021/acsinfecdis.5b00031. Epub, 2015 Jun 18. PMID:27622821^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.