Pyridine coupled pyrazole analogues as lethal weapon against MRSA: An in-vitro and in-silico approach

Abstract

The treatment of Methicillin-resistant staphylococcus aureus (MRSA) infections has become challenging due to the growth of multidrug resistance in the bacteria. Here we report the synthesis of pyridine-coupled pyrazoles as an antimicrobial agent against MRSA. A series of pyridine coupled pyrazoles were synthesized and synthesized compounds were characterized using FT-IR, ¹H NMR, and Mass spectroscopy. The ADMET results of all the 14 active compounds are interpreted. To identify the potent compound the synthesized compounds screened for minimum inhibitory concentrations against MRSA and compared with standard drug vancomycin. Among the synthesized compounds 6d exhibited good antibacterial activity with MIC value 21 μg/mL, bacterial cell membrane damage study was studied potassium efflux, and cellular content leakage assay. Anticoagulant study for the potent compound also studied and validated by molecular docking and molecular dynamics simulation studies. The docking study of the synthesized compound was carried out and the study depicted that the pyridine ring of all the analogues binds with the various amino acids in the binding pocket of the active site of the Staphylocoagulase and PBP2a protein of MRSA.

Keywords: MRSA; Molecular docking; Molecular dynamics; PBP2a; Pyrazole; Pyridine; Staphylocoagulase.