Synthesis Of Chrysin Amino Acid Derivatives Bridged By Bromohexanoate And Their Anti-tumor Activity Of MGC-803 And MCF-7

Objective:To design and synthesize a series of chrysin derivatives by using chrysin as a starting material and to explore its anti-proliferative effect on cancer cells in vitro.Through the structural modification,it is expected to obtain higher therapeutic effect than the parent compound,and low toxicity,good selectivity of the anticancer lead compounds,so as to provide a strong theoretical basis for further exploration and development of anticancer drugs.Methods:Chrysin derivatives were synthesized by four-step reaction,substitution,hydrolysis,amide condensation and re-hydrolysis.The structures of the synthesized chrysin derivatives were confirmed by melting point(M.P.),nuclear magnetic resonance(NMR)and mass spectrometry(MS).Through using the MTT assay to test the chrysin derivatives inhibitory effects on the proliferation of human gastric cancer MGC-803 cell and human breast cancer MCF-7 cell.Results:Twenty-eight chrysin derivatives(compounds 2-29)were synthesized,of which 27 compounds were the first reported new compounds.The structure of all compounds were confrimed by using melting points(M.P.),nuclear magnetic resonance(NMR),Mass spectrometry(MS)and so on.In the tested compounds,MTT assay results show that,compounds 7,9,14,15,16,23 displayed potent MGC-803 inhibitory activity with IC50 values of 24.50 μmol·L-1,27.54μmol·L-1,30.87 μmol·L-1,43.64 μmol·L-1,24.30 μmol·L-1,24.61μmol·L-1,which inhibitory concentrations lower than the parent compound chrysin(IC50=47.8 μmol·L-1),and the compounds 7,9,14,16,23 inhibitory concentrations is comparable to the positive medicine 5-FU(IC50 =39.2 μmol·L-1).Most of the compounds displayed MCF-7 inhibitory activity with IC50 values are lower than the chrysin(IC50=143.4μmol·L-1),especially the compounds 12,15 inhibitory concentrations is comparable to the positive medicine 5-FU(IC50=29.15 pmol·L-1).Conclusion:A series of chrysin derivatives(2-29)were synthesized by the method of substitution,hydrolysis,amide condensation and rehydrolysis.The MTT assay results showed that the in vitro anti-Gastric cancer MGC-803 cell line,anti-breast cancer MCF-7 cell line had better effect of the chrysin derivatives,which provides a new idea for the synthesis of new drugs in the form of chrysin derivatives.