Design, synthesis, in-vitro anticancer evaluation and in-silico molecular docking studies of 1,2,3-triazole incorporated 1,3,5-triazin-2-yl)quinazolin-2-yl derivatives

A new series of 1,2,3-triazole incorporated 1,3,5-triazin-2-yl)quinazolin-2-yl (29a-j) derivatives and evaluated for their anticancer activity against four human cancer cell lines such as human prostate cancer (PC3), human lung cancer (A549), human breast cancer (MCF-7) & human ovarian cancer (A2780) by using of MTT method. The most of the screened derivatives displayed remarkable anticancer activities with IC50 values ranges from 0.03 ± 0.0076 µM to 6.73 ± 1.98 µM, whereas, standard drug, etoposide showed anticancer activities ranges from 1.38 ± 0.56 µM to 3.08 ± 0.135 µM. Among them, six compounds 29a, 29b, 29c, 29d, 29e and 29j was displayed more potent activities than positive control. Among them, compound 29a showed potent anticancer activities against PC3, A549, MCF-7, and A2780 cell lines with IC50 values of 0.19 ± 0.061 µM; 0.03 ± 0.0076 µM; 0.11 ± 0.065 µM & 0.34 ± 0.043 µM respectively. Docking studies against human Topoisomerase IIβ, EGFR, and VEGFR2 revealed strong binding affinity toward VEGFR2 (−10.7 to −9.7 kcal/mol), with compounds 29a, 29d, and 29e showing comparable interactions to the reference inhibitor Tivozanib. EGFR affinities (−8.9 to −7.8 kcal/mol) exceeded Erlotinib, while Topoisomerase IIβ binding was moderate (−5.8 to −5.2 kcal/mol). Detailed interaction analysis indicated conserved hydrogen bonding, π–π stacking, and hydrophobic contacts, resembling the binding patterns of established inhibitors. Overall, compounds 29a, 29d, and 29e demonstrated dual-target engagement and promising binding interaction profiles, supporting their further optimization as broad-spectrum anticancer candidates.