Synthesis, characterization and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and EGFR downregulation

Abstract

Chrysin amino acid derivatives were synthesized to evaluate for their antiproliferative activities. Among them, N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)valeryl)-L-leucine (8c) displayed the most remarkable inhibitory activities against MCF-7 cells with IC₅₀ values of 16.6 μM. Preliminary mechanistic studies showed that 8c could inhibit the colony formation and migration of MCF-7 cells. Flow cytometry analysis demonstrated that 8c mediated cell apoptosis and the prolongation of cell cycle progression in G1/S-phase against MCF-7 cells. Besides, 8c displayed the moderate inhibition against EGFR. Western blot assay suggested that 8c significantly inhibited EGFR phosphorylation. Molecular docking showed that 8c can bind the EGFR kinase well.

Keywords:

• Chrysin derivatives
• EGFR
• amino acid
• antitumor

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

We are grateful to the Hunan Provincial Department of Education Key Project (18A244), the University of South China Students Research Learning and Innovative Experimental Project (2018XJXZ200),Graduate student science foundation of University of South China (2018496) and the University of South China Students Research Learning and Innovative Experimental Project (2018XJXZ359) for financial support.