Synthesis, Characterization And Anti-cancer Evaluation Of Amino Acid Derivatives Containing Chrysin

Objective: In order to search for the anti-cancer drugs with high efficacy, lowtoxicity, and minimum side effects and provide a theoretical basis for the discovery ofnew anti-cancer drugs, series of novel amino acid derivatives containing chrysin weresynthesized.Methods: Series of novel chrysin derivatives were synthesized by halogenation,hydrolysis and condensation and evaluated for anti-proliferative activity on humangastric carcinoma cell line MGC-803and human hepatocellular carcinoma cell lineHepG2by MTT (methyl thiazolyl tetrazolium)-based Assay. Based on the screeningresults of cell proliferative activities, we detected the apoptosis induction of thesynthetic chrysin derivatives with the better potent-inhibitory effect compared to thepositive control cisplatin against MGC-803cells by flow cytometry and western blot.Results:28chrysin derivatives were synthesized and the structures of thesecompounds were assigned by NMR and MS. From the bioassay results, most of thesynthetic compounds displayed a moderate-good degree of anti-cancer activity,especially that the compoundN-[4-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)butyryl]–L-isoleucine methylester(20) exhibited the most potent inhibitory activity with IC50(half maximalinhibitory concentration) value of3.23μmol/L. FCM assay demonstrated thatcompound20could induce the apoptosis of MGC-803cells in a dose dependentmanner and western blot assay indicated that20could induce the apoptosis throughincreasing protein expression of Bax and decreasing protein expression of Bcl-xl.Conclusion: Series of novel chrysin derivatives were synthesized, which expandedthe research category of chrysin derivatives. The anti-cancer activities of all thesynthetic compounds were evaluated and we explored probable molecular mechanism of anti-cancer activities of compounds, which could be further used to guide therational design drug candidates with inducing apoptosis of cells.