Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

Back

Recent Advances in the Discovery of Metallo-β--Lactamase Inhibitors for β-lactam Antibiotic-Resistant Reversing Agents

Author(s): Zhenzhen Guo and Shutao Ma

Affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, P. R. China.

Keywords: Antibiotic, β-lactam, inhibitor, metallo-β-lactamase, resistant and zinc enzyme.

Abstract:

The overuse of antibiotics which exerts the selective pressure for bacterial pathogens has facilitated the spread of antibiotics’ resistance. Metallo-β-lactamases (MβLs) are zinc enzymes produced by an increasing number of bacterial pathogens. They can readily cleave carbapenems and most other β-lactams that are mainstays of therapy for bacterial infections. MβL-conferred resistance to antibiotics is most worrisome due to MβLs exhibiting very broad-spectrum resistance. Therefore, the bacteria carrying MβLs have recently become a significant clinical threat. No clinically useful MβLs inhibitor has been discovered yet. To address the serious threat to public health posed by the MβL-conferred resistance to antibiotics, novel effective MβL inhibitors are urgently needed. This review mainly describes various MβL inhibitors, giving special attention to their antibacterial activity, mechanisms of action, structure-activity relationships and synergetic effect with clinically available antibiotics.

Reprint ePrint Rights & PermissionsPrintExport

Article Details

VOLUME: 15
ISSUE: 7
Page: [689 - 702]
Pages: 14
DOI: 10.2174/1389450115666140326094504