Synthesis and investigation of inhibitory activities of imidazole derivatives against the metallo-β-lactamase IMP-1

Mutations in bacteria can result in antibiotic resistance due to the overuse or abuse of beta-lactam antibiotics. One strategy which bacteria can become resistance toward antibiotics is secreting of metallo beta-lactamase enzymes that can open the lactam ring of the beta-lactam antibiotic and inactivate them. This issue is a threat for human health and one strategy to overcome this situation is co-administration of beta-lactam antibiotics with an inhibitor. So far, no clinically available inhibitors of metallojilactamases (MBLs) reported and the clinically inhibitors of serine beta-lactamase are useless for MBL5. Accordingly, finding a potent inhibitor of the MBL5 being very important. In this study, imidazole derivatives primarily were synthesized and their inhibitory activity were measured. Later in silico binding model was used to predict the configuration and conformation of the ligands into the active site of enzyme. Two molecules demonstrated with IC50, of 39 mu M and 46 mu M against MBL (IMP-1).