Green Synthesis, In Silico Molecular Docking, and Evaluation of Pyrazole Derivatives for Their Antifungal and...

A series of 25 pyrazole derivatives was synthesized via ultrasonication-assisted cyclization of chalcones with phenylhydrazine and characterized using ¹H NMR, ^{1 3}C NMR, and LC-HRMS. Biological evaluation revealed that P-25 [5-(4-fluorophenyl)-1,3-diphenyl-1H-pyrazole] exhibited the highest antifungal activity against Rhizoctonia solani (ED₅₀ = 5.56 µg mL^{- 1}), approaching the efficacy of positive control hexaconazole 5% SC (ED₅₀ = 3.67 µg mL^{- 1}). While P-6 [5-(3-nitrophenyl)-1,3-diphenyl-1H-pyrazole] was most effective against Fusarium oxysporum (ED₅₀ = 301.5 µg mL^{- 1}). In nematicidal assays, P-21 [3-(4-ethoxyphenyl)-5-(4-nitrophenyl)-1-phenyl-1H-pyrazole] showed the greatest activity against Meloidogyne incognita (LC₅₀ = 31.25 µg mL^{- 1}, 24 h) although less potent than fluopyram 34.48% SC (Velum Prime) (LC₅₀ = 3.46 µg mL^{- 1}). Molecular docking studies targeting succinate dehydrogenase (SDH) supported the experimental results, with P-6, P-25, and P-21 exhibiting the strongest binding affinities against SDH of F. oxysporum (-8.3 kcal mol^{- 1}), R. solani (-8.3 kcal mol^{- 1}), and M. incognita (-7.7 kcal mol^{- 1}), respectively.