title: Recent advances in the discovery of metallo-β-lactamase inhibitors for β-lactam antibiotic-resistant reversing agents.
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.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, P. R. China. mashutao@sdu.edu.cn.
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry*; D018440:beta-Lactam Resistance / Q000187:drug effects*; D065093:beta-Lactamase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D015032:Zinc