Design, Synthesis, Molecular Docking, and Anticancer Activity of Chalcone Derivatives as VEGFR-2 Inhibitors

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. Compounds2r,2o, and2lexhibited remarkable cytotoxicity against K562, SiHa, and B16 cells, with IC50values of 0.97 μM, 1.22 μM, and 1.39 μM, respectively. Moreover, compound2lexhibited potent cytotoxicity against K562, SiHa, and B16, with IC50values ranging from 1.25 μM to 1.39 μM. Compounds2land2oalso exhibited excellent inhibitory activity on VEGFR-2 kinase, with IC50values 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 compound2linduced apoptosis and arrested the cell cycle at the G1 and S phases.