Design, synthesis, antimicrobial evaluation, and molecular docking studies of novel biphenyl-bearing pyrazole derivatives

In this work, a novel series of biphenyl-based pyrazole compounds (4a–4g) was successfully prepared and their structures were confirmed using standard spectroscopic methods like FT-IR, 1 H NMR, 13 C NMR, and HRMS. Biological testing confirmed that 4g showed excellent antibacterial activity with very low MIC values of 0.52 µg/mL against Staphylococcus aureus and 0.85 µg/mL against Escherichia coli . Remarkably, compound 4g stood out for its strong antifungal action, giving a 41 mm inhibition zone against Aspergillus flavus , similar to standard antifungal drugs. It also showed high activity against Gram-negative bacteria, with a 38 mm inhibition zone against Pseudomonas vulgaris . The strong performance of 4 g may be due to its multi-heteroatom outline and extended π-conjugation, which help in forming dual interactions with microbial targets. Docking studies also showed that pyrazole 4g had the best interaction with the Escherichia coli FabB enzyme (ΔG = − 9.6 kcal/mol), mainly because of its high heteroatom content, which supported strong hydrogen bonding and hydrophobic interactions. Overall, these findings suggest that biphenyl-based pyrazole derivatives, especially 4g is promising candidates for developing new broad-spectrum antimicrobial agents.