Synthesis, Anticancer, and Molecular Docking Studies of 3-Benzyl-N-aryl-1H-1,2,4-triazol-5- amines

Six new triazole analogues (4a-f) and the antiproliferative activity of four analogues have been described in this study. The triazoles were synthesized in three steps starting from aromatic anilines. A series of six triazoles were synthesized, and their structures (4a-f) were confirmed using nuclear magnetic resonance and mass spectral data, followed by anticancer testing of four compounds at 10 µM against nine different panels of human cancer cell lines using the National Cancer Institute (NCI US) standard protocol. All the four compounds were found to have moderate to low antiproliferative activity. 3-Benzyl-N-(2,5-dimethoxyphenyl)-1H-1,2,4-triazol-5-amine (4d) was discovered to have significant antiproliferative activity with higher sensitivity toward NCI-H522, MOLT-4, PC-3, HL-60(TB), HT29, CCRF-CEM, UO-31, UACC-257, and A549 cell lines with percent growth inhibitions (GIs) of 32.59, 26.53, 23.03, 21.84, 19.81, 17.97, 12.70, 12.29, and 12.19, respectively. The binding affinities of the title ligands (4a-f) against the colchicine binding site of tubulin were investigated using a molecular docking simulation. All of the ligands had similar types of binding interactions (H-bond interaction between the residue Ala317 and NH function of triazole), with the exception of ligand 4d, which had two H-bonds (Asn258; NH function of triazole and secondary amine function) and a π-cationic interaction with the residue Lys254 and triazole ring.