Design, synthesis, and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and suppress cell migration

Abstract

Amino acid derivatives containing chrysin were synthesized for evaluating their anticancer effects. Among them, compound N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)heptanoyl)-L-isoleucine (6e) displayed the most potent antiproliferative activity against MGC-803 cells with IC₅₀ value of 20.0 μM. Preliminary mechanistic studies showed that compound 6e could inhibit the colony formation and migration of MGC-803 cells. Flow cytometry analysis demonstrated that compound 6e mediated cell apoptosis of MGC-803 cells and arrested cell cycle in G2/M-phase. Moreover, 6e treatment in MGC-803 cells downregulated anti-apoptotic protein Bcl-2 and upregulated pro-apoptotic gene Bax in a concentration-dependent manner. Our studies suggest that compound 6e may sever as an effective chemotherapeutic candidate.

Keywords:

• Chrysin derivatives
• amino acid
• anticancer
• apoptotic

Acknowledgements

Our deepest gratitude goes first and foremost to Professor Amy Schwarber and Doctor Yuhua Wang from Cincinnati children hospital and medicine center for their proofreading work.

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

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