Diaryl-Substituted Azolylthioacetamides: Inhibitor Discovery of New Delhi Metallo-β-Lactamase-1 (NDM-1)

• Published in: ChemMedChem 2014-11, Vol.9 (11), p.2445-2448
• Main Authors: Zhang, Yi-Lin, Yang, Ke-Wu, Zhou, Ya-Jun, LaCuran, Alecander E., Oelschlaeger, Peter, Crowder, Michael W.
• Format: Article
• Language: English
• Subjects: Acetamides - chemistry; Acetamides - metabolism; Aeromonas - enzymology; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibiotic resistance; antibiotics; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Bacteroides fragilis - enzymology; beta-Lactamases - chemistry; beta-Lactamases - metabolism; Binding Sites; Drug Resistance, Bacterial - drug effects; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; inhibitors; Kinetics; metallo-β-lactamases; Molecular Docking Simulation; NDM-1; Protein Structure, Tertiary; Stenotrophomonas maltophilia - enzymology
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201402249

The emergence and spread of antibiotic‐resistant pathogens is a global public health problem. Metallo‐β‐lactamases (MβLs) such as New Delhi MβL‐1 (NDM‐1) are principle contributors to the emergence of resistance because of their ability to hydrolyze almost all known β‐lactam antibiotics including penicillins, cephalosporins, and carbapenems. A clinical inhibitor of MBLs has not yet been found. In this study we developed eighteen new diaryl‐substituted azolylthioacetamides and found all of them to be inhibitors of the MβL L1 from Stenotrophomonas maltophilia (Ki