Synthesis of Triazole-Substituted Quinazoline Hybrids for Anticancer Activity and a Lead Compound as the EGFR Blocker and ROS Inducer Agent

A series of triazole-substituted
quinazoline hybrid compounds were
designed and synthesized for anticancer activity targeting epidermal
growth factor receptor (EGFR) tyrosine kinase. Most of the compounds
showed moderate to good antiproliferative activity against four cancer
cell lines (HepG2, HCT116, MCF-7, and PC-3). Compound 5b showed good antiproliferative activity (IC50 = 20.71
μM) against MCF-7 cell lines. Molecular docking results showed
that compound 5b formed hydrogen bond with Met 769 and
Lys 721 and π–sulfur interaction with Met 742 of EGFR
tyrosine kinase (PDB ID: 1M17). Compound 5b decreases the expression
of EGFR and p-EGFR. It also induces apoptosis through reactive oxygen
species generation, followed by the change in mitochondrial membrane
potential.