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

Abstract

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

Graphical abstract

Keywords:

• Chrysin derivatives
• amino acid
• apoptosis
• breast cancer
• cell viability

Acknowledgments

We are grateful to the The Hunan Natural Science Foundation Project (2018JJ2349), the University of South China Students Research Learning and Innovative Experimental Project (2018147200) and Graduate student science foundation of University of South China (2018496) for financial support.

Disclosure statement

No potential conflict of interest was reported by the authors.