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

ABSTRACT

Mutations in bacteria can result in antibiotic resistance due to the overuse or abuse of ß-lactam antibiotics. One strategy which bacteria can become resistance toward antibiotics is secreting of metallo ß-lactamase enzymes that can open the lactam ring of the ß-lactam antibiotic and inactivate them. This issue is a threat for human health and one strategy to overcome this situation is co-administration of ß-lactam antibiotics with an inhibitor. So far, no clinically available inhibitors of metallo ß-lactamases (MBLs) reported and the clinically inhibitors of serine ß-lactamase are useless for MBLs. Accordingly, finding a potent inhibitor of the MBLs 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 µM and 46 µM against MBL (IMP-1).