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

<p>A new series of 1,2,3-triazole incorporated 1,3,5-triazin-2-yl)quinazolin-2-yl (<b>29a-j</b>) 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 <b>29a, 29b, 29c, 29d, 29e</b> and <b>29j</b> was displayed more potent activities than positive control.

Among them, compound <b>29a</b> 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 <b>29a, 29d,</b> and <b>29e</b> showing comparable interactions to the reference inhibitor Tivozanib.