Design, Synthesis, and Anticancer Activity of New Quinazoline Derivatives as VEGFR-2 Inhibitors and Apoptosis Inducers

Abstract— A new series of thiourea or thioacetamide linked quinazoline derivatives has been synthesized and tested for cytotoxicity against the HCT116 and MCF-7 cell lines. Compound 10b, demonstrates strong antiproliferative effect against both colon HCT-116 and MCF-7 cell lines. Compound 10b interrupts the HCT-116 cell cycle at the G2/M phase. According to DNA flow cytometry and annexin test, hybrid 10b is also capable of inducing cell cycle disruption and apoptosis in HCT-116 cells. It causes apoptosis by activating caspases-3, increasing proapoptotic Bax and p53 levels, and decreasing Bcl-2 protein levels. As a result, the novel derivative 10b may be regarded as a promising lead to antitumor agents development.