title: 3-mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-β-lactamase inhibitors.
abstract: The production of β-lactamases is an effective strategy by which pathogenic bacteria can develop resistance against β-lactam antibiotics. While inhibitors of serine-β-lactamases are widely used in combination therapy with β-lactam antibiotics, there are no clinically available inhibitors of metallo-β-lactamases (MBLs), and so there is a need for the development of such inhibitors. This work describes the optimisation of a lead inhibitor previously identified by fragment screening of a compound library. We also report that thiosemicarbazide intermediates in the syntheses of these compounds are also moderately potent inhibitors of the IMP-1 MBL from Pseudomonas aeruginosa. The interactions of these inhibitors with the active site of IMP-1 were examined using in silico methods.
authors: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, Qld 4072, Australia.
authors: Faridoon
authors: Waleed M
authors: WM
authors: Hussein
authors: Peter
authors: P
authors: Vella
authors: Nazar Ul
authors: NU
authors: Islam
authors: David L
authors: DL
authors: Ollis
authors: Gerhard
authors: G
authors: Schenk
authors: Ross P
authors: RP
authors: McGeary
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006801:Humans; D007700:Kinetics; D008670:Metals / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D012663:Semicarbazides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D065093:beta-Lactamase Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D008670:Metals; D012663:Semicarbazides; D014230:Triazoles; D065093:beta-Lactamase Inhibitors; C005151:thiosemicarbazide