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

• Published in: Russian journal of bioorganic chemistry Vol. 45; no. 5; pp. 381 - 390
• Main Authors: Siliveri, Sravanthi, Harinadha Babu Vamaraju, Raj, Shiva
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.09.2019; Springer Nature B.V
• Subjects: Benzene; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Chemical synthesis; Hydrocarbons; Life Sciences; Molecular docking; Organic Chemistry; Pyrazole; Spectral methods; Sulfonamides; Triazoles; docking; PI3Kα; cancer; ADMET; malignant
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162019050108

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)-1 H -1,2,3-triazol-4-yl)-5-(4-nitro phenyl)-4,5-dihydro-1 H -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 IC 50 value ranging from 6 to 25 µg/mL.