Design, synthesis and 3D-QSAR study of cytotoxic flavonoid derivatives

Three series of flavonoid derivatives were designed and synthesized. All synthesized compounds were evaluated for cytotoxic activities against five human cancer cell lines, including K562, PC-3, MCF-7, A549, and HO8910. Among the compounds tested, compound 9d exhibited the most potent cytotoxic activity with IC50 values of 2.76–6.98μM. Further comparative molecular field analysis was performed to conduct a 3D quantitative structure–activity relationship study. The generated 3D-QSAR model could be used for further rational design of novel flavonoid analogs as highly potent cytotoxic agents.