Evaluation of Next Generation ?lactam Inhibitors against Penicillinase Producing Methicillin-Resistant Staphylococcus aureus - Abstract
Antibiotics are indispensable drugs in curing pathogenic bacteria that cause deadly diseases and infections. A plethora of antibiotics are available in different classes, however, ?lactam inhibitors are one of the oldest class of inhibitors against manygram-positive as well as gram-negative bacteria. Pathogens are becoming more powerful, gradually developing resistance against successful ?lactam antibiotics. Therefore, synthesis of novel ?lactam inhibitors is a fundamental process in drug discovery. This study focused on the Methicillin-Resistant Staphylococcus (MRSA) that produces penicillinase: PBP3. We identified 14 popular ?lactam inhibitors: Ceftobiprole, Clavulanate, Sulbactam, Tazobactam, Biapenem, Razupenem, LK-157, Ceftolozane, Ampicillin, Amoxicillin, Ticarcillin, Piperacillin, Penicillin G, and Cefotaxime. Amongthem, Clavulanate, Sulbactam, and Tazobactam are next generation ?lactam antibiotics. Molecular docking was carried out between MRSA-PBP3 and ?lactam inhibitors in order to report the potential ligand. Interestingly, we found Clavulanate – a next generation antibiotic along with ther leading molecule in a row (Sulbactam, and Tazobactam) – has shown least binding affinity when compared with reference molecule Penicillin-G. Despite Clavulanate effectively acting against MRSA, its binding stability is less in MRSA-PBP3 complex. Therefore this study suggesting improved analogs are required to strengthen binding interaction alongside active against resistant bacteria.