• Novel biphenyl–heterocyclic pyrazole frameworks (4a–4 h) designed and synthesized. • Structures validated via FT-IR, NMR, and HRMS analyses. • Docking against Escherichia coli DNA gyrase B revealed strong binding (ΔG up to –7.7 kcal/mol). • Key stabilizations from H-bonding and hydrophobic interactions identified via docking. • Pyrazoles 4f showed potent broad-spectrum antimicrobial activity (MIC 7.25 and 13.5 µg/mL). The growing threat of antimicrobial resistance necessitates the development of new and effective antimicrobial agents. In this study, a series of heterocyclic biphenyl-resultant novel pyrazole scaffolds were rationally designed and synthesized using an efficient synthetic protocol. The chemical structures of the synthesized compounds were confirmed by standard spectroscopic techniques, including NMR and mass spectrometry. The antimicrobial activity of the prepared pyrazole derivatives was evaluated in vitro against selected Gram-positive and Gram-negative bacterial strains. Minimum inhibitory concentration (MIC) values were determined to quantify their antimicrobial potency. Pyrazole 4f displayed promising antibacterial and antifungal activity with low MIC values of 7.25 and 13.51 µg/mL respectively, indicating strong growth inhibition compared to standard reference drugs. To support the experimental findings, molecular docking studies were performed against key bacterial target enzymes to investigate ligand–protein interactions. The docking results revealed favourable binding conformations, supported by hydrogen bonding and hydrophobic interactions within the active sites, which showed good correlation with the observed MIC data. Structure–activity relationship analysis highlighted the importance of the pyrazole framework and heterocyclic substitutions in enhancing antimicrobial efficacy. Overall, the present work demonstrates that heterocyclic biphenyl-based pyrazole scaffolds are promising lead candidates for the development of potent antimicrobial agents and provide valuable insights for future medicinal chemistry optimization.
Kasundra et al. (Wed,) studied this question.