Exploring Pyrazole‐Imidazole Chalcone Hybrids: Synthesis, Characterization, Antifungal Activity, DFT Calculations, and In Silico Analysis
Keshav B. Gangurde, Vishnu A. Adole, Hemant S. Deshmukh, Suraj N. Mali, R. Rajesh, Pramod Patil, Dattatray S. GhotekarABSTRACT
A novel library of imidazole–pyrazole hybrid chalcones ( 3a–3n ) was synthesized via Claisen–Schmidt condensation using 5‐(1H‐imidazol‐1‐yl)‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde and diverse ketones. The structures were confirmed by FT‐IR, 1 H NMR, 1 3 C NMR, and HRMS techniques. Antifungal screening against Candida albicans revealed potent activity for 3b , 3c , 3d , 3k , and 3l , with 3b showing the highest inhibition (45 mm), highlighting the impact of para‐electron‐donating groups. Molecular docking with lanosterol‐14α‐demethylase (PDB ID: 5HS1) showed strong binding affinities, with 3i giving the best docking score (−8.36 kcal/mol). DFT (B3LYP/6‐31G(d,p)) confirmed stable π‐conjugated geometries across chalcone bridge. Compound 3b displayed key H‐bond interactions supporting its selective antifungal effect. ADME profiling indicated favorable pharmacokinetic properties, underscoring the potential of these compounds for further development as antifungal drugs.