Pyridine coupled pyrazole analogues as lethal weapon against MRSA: An in-vitro and in-silico approach. (May 2022)

• Record Type: Journal Article
• Authors: Nanjundaswamy, S.; Jayashankar, J.; Renganathan, R.R. Arun; Karthik, C.S.; Mallesha, L.; Mallu, P.; Rai, V. Ravishankar
• Is Part Of: Microbial pathogenesis. Volume 166(2022)
• Publication Date: 2022-05
• Subjects: Pyrazole -- Pyridine -- MRSA -- Molecular docking -- Molecular dynamics -- Staphylocoagulase -- PBP2a; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2022.105508
• Languages: English
• ISSNs: 0882-4010

Abstract

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, 1 H 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. Graphical abstract: Image 1 Highlights: Pyrazole dipyridine analogues were successfully synthesized and characterized. The potent Pyrazole dipyridine was designed and synthesized to treat infectious agent MRSA. Evaluated for antibacterial activity, anti-coagulase and anti-biofilm of potent analogue against MRSA was studied. Molecular docking, molecular dynamics simulation were performed for PBP2a and Staphylocoagulase.