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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
DOI: 10.2174/1389450115666140326094504      Price:  $58

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

Author(s): Zhenzhen Guo and Shutao Ma
Pages 689-702 (14)
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.
Antibiotic, β-lactam, inhibitor, metallo-β-lactamase, resistant and zinc enzyme.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, P. R. China.