Reline-Based DES-Assisted Synthesis of C3-Indole-Pyrazole Schiff Bases: Integrated Antioxidant, Antibacterial and Molecular Docking Studies

Abstract A series of indole–pyrazole Schiff base conjugates was synthesized and biologically evaluated, revealing notable antioxidant and antibacterial activities. In free radical scavenging assays, several derivatives exhibited concentration-dependent efficacy, with specific fluorinated, nitrated and methoxy substituted analogues demonstrating the strongest antioxidant performance in both DPPH and hydrogen peroxide scavenging assays, achieving high levels of radical inhibition at 5 mg/mL relative to standard ascorbic acid. Antibacterial screening against S. aureus, E. coli, P. polymyxa, and P. aeruginosa identified key active derivatives exhibiting substantial growth inhibition across multiple strains, with P. aeruginosa displaying exceptional sensitivity. Molecular docking studies corroborated the experimental findings, demonstrating favorable binding interactions of the lead compounds within the active sites of bacterial DNA gyrase targets. Notably, the 4-fluorobenzylidene derivative displayed the highest binding affinity toward both S. aureus DNA gyrase and P. aeruginosa DNA gyrase B, driven by strong and stable ligand–protein interactions. Validation of the docking protocol via self-docking of co-crystallized ligands yielded acceptable root-mean-square deviation (RMSD) values (<3 Å), confirming the predictive reliability of the computational model. Overall, the integrated biological and computational insights underscore the lead fluoro-substituted hybrid as a promising multifunctional candidate, demonstrating that strategic aryl ring substitutions on the indole–pyrazole framework critically modulate both antioxidant and antibacterial potency.