Abstract
A series of 4-phenylurea chalcones (2a-2s) as VEGFR-2 inhibitors has been designed, synthesized, and evaluated for in vitro cytotoxic activity against K562, SiHa, and B16 cancer cells. Compared to sorafenib, the compounds exhibited strong cytotoxicity against K562, SiHa and B16 cells. Compounds 2r, 2o, and 2l exhibited remarkable cytotoxicity against K562, SiHa, and B16 cells, with IC(50) values of 0.97 μM, 1.22 μM, and 1.39 μM, respectively. Moreover, compound 2l exhibited potent cytotoxicity against K562, SiHa, and B16, with IC(50) values ranging from 1.25 μM to 1.39 μM. Compounds 2l and 2o also exhibited excellent inhibitory activity on VEGFR-2 kinase, with IC(50) values of 0.42 ± 0.03 and 0.31 ± 0.02 μM, respectively. Molecular docking proved that the target compounds had strong binding interactions with VEGFR-2 proteins. Flow cytometry analysis showed that compound 2l induced apoptosis and arrested the cell cycle at the G1 and S phases.