Design and Development of Pyrazole Schiff Bases Against MRSA: Synthesis, Spectral, and Biological Studies Infections

Abstract

This study reports the design and synthesis of a series of pyrazole Schiff bases and their evaluation as potential antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). The compounds were synthesized via condensation of pyrazole amines with aromatic aldehydes and characterized using FT-IR, NMR, and elemental analysis. Pharmacophore modeling and ADMET predictions indicated favorable pharmacokinetic properties. Among the synthesized derivatives, compound 7i showed the most promising results, with a docking score of -7.4 kcal/mol against the PBP2a enzyme of MRSA and a binding free energy of -42.8 kcal/mol from MM-GBSA calculations. Molecular dynamics simulations confirmed the stability of the 7i-PBP2a complex, while density functional theory (DFT) analysis revealed a HOMO-LUMO gap of 4.28 eV, indicating strong stability and reactivity. Antibacterial studies demonstrated that compound 7i exhibited a minimum inhibitory concentration (MIC) of 84 µg/mL and a zone of inhibition of 10 mm at 100 µg, highlighting measurable activity against MRSA. Compared with standard antibiotics, these results suggest that pyrazole Schiff bases, particularly compound 7i, represent a novel structural class with potential as lead molecules for the development of new anti-MRSA agents.

Keywords: Pyrazole Schiff base, MRSA, Molecular docking, Molecular dynamics simulation, Drug design