Synthesis and biological evaluation of amino acid derivatives containing chrysin that induce apoptosis.

A series of chrysin amino acid derivatives were synthesized to evaluate for their antiproliferative activities against several cancer cell lines. Among the compounds tested, -(2-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)octanoyl)--leucine methyl ester() presented a good anti-proliferative activity in MDA-MB-231 and MCF-7 cells. Flow cytometry analysis showed that induced apoptosis and prolonged cell cycle progression in MDA-MB-231 and MCF-7 cells. Western blot analysis showed that significantly inhibited Akt phosphorylation (Ser473) in MDA-MB-231 and MCF-7 cells. In addition, treatment markedly downregulated Bcl-2 and upregulated Bax in a dose-dependent manner. caspase activation assay showed that induced apoptosis of MDA-MB-231 cells by enhancing caspase 3/7 activity. The regulatory effect of on apoptosis of MDA-MB-231 and MCF-7 cells may be induced by mitochondrial apoptosis pathway. This study is of great significance for designing and developing more effective chrysin amino acid derivatives.