Boronic acid inhibitors of the class A β-lactamase KPC-2. Issue 11 (15th July 2018)

• Record Type: Journal Article
• Authors: Zhou, Jingyuan; Stapleton, Paul; Haider, Shozeb; Healy, Jess
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 11(2018)
• Page Start: 2921
• Page End: 2927
• Publication Date: 2018-07-15
• Subjects: KPC -- Beta-lactamase -- Antibiotic resistance -- Boronic acid inhibitors; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.04.055
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The rapid rise of antimicrobial resistance is one of the greatest challenges currently facing medical science. The most common cause of resistance to β-lactam antibiotics is the expression of β-lactamase enzymes, such as KPC-2. As such the development of novel inhibitors of KPC-2 and related enzymes is of the upmost importance. We report the design and synthesis of novel boronic acid transition state analogs containing a 1, 4-substituted 1, 2, 3-triazole linker based on the known inhibitor 3-nitrophenyl boronic acid and demonstrate that they are promising scaffolds for the development inhibitors of KPC-2 with the ability to recover sensitivity to the antibiotic cefotaxime.