Design, Synthesis, Molecular Docking, ADMET Studies, and Biological Evaluation of Isoxazoline and Pyrazoline Incorporating 1,2,3-Triazole Benzene Sulfonamides¹

Abstract—In targeted therapy of cancer, PI3Kα targeting is being considered as a promising approach to design novel anticancer drugs. In the present work we report a novel series of isoxazoline and pyrazoline incorporated 1,2,3-triazole benzene sulphonamides with their design, synthesis, molecular docking, ADMET, and in vitro anti-proliferative studies. The synthesized compounds were characterized by physical and spectral methods. Among all the synthesized compounds N-Methyl-3-(5-methyl-1-(4-sulfamoylphenyl)-1H-1,2,3-triazol-4-yl)-5-(4-nitro phenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (Vm) showed good binding affinity to the active site of PI3Kα with a docking score of 137.05 having better ADMET profile. Eleven compounds were screened for anti-proliferative activity; four of them showed substantial cytotoxic activity with IC₅₀ value ranging from 6 to 25 µg/mL.