Synthesis, Antifungal Activity, Molecular Docking, Aquatic Toxicity Prediction and 2D-QSAR of Pyrazole Derivatives as...

The major problems in basmati rice are sheath blight and bakanae diseases caused by Rhizoctonia solani and Fusarium fujikuroi, which significantly lower the productivity of basmati rice. However, the excessive use of fungicides can result in pathogen resistance, environmental overload and mammalian toxicity. Therefore, there is a need for new fungicides with novel modes of action, low toxicity and minimal residue. To address this, 20 pyrazole derivatives from alkoxy/halo acetophenones and N,N-dimethylformamide dimethyl acetal are synthesized and characterized by various techniques, namely, ¹H NMR, ¹³C NMR and LC-HRMS, expressing fungicidal activity against R. solani and F. fujikuroi. Compound 5r (3-(5-fluoro-2-hydroxylphenyl) pyrazole) exhibited the highest activity (ED₅₀ = 2.75 µg mL^-1) against both R. solani and F. fujikuroi. 2D-quantitative structure-activity relationship (2D-QSAR) analysis, particularly MLR (Model 1), with a strong correlation coefficient (r²) of 0.973, a cross-validated correlation coefficient (q²) of 0.84, and an $r_{\mathrm{pred}}^2$ of 0.93, highlighted AI descriptors T_2_F_6, T_2_Cl_7, T_T_O_4 and DeltaAlphaA, the key descriptors influencing fungicidal activity. Molecular docking studies revealed the potential of these pyrazole derivatives as novel fungicides as succinate dehydrogenase inhibitors (SDHI), suggesting valuable reference for design of effective fungicides.