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


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.


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.

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

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Article Details

Page: [689 - 702]
Pages: 14
DOI: 10.2174/1389450115666140326094504