Synthesis And Anticancer Activity Of HepG2?MCF-7 Of Chrysin Amino Acids Derivatives Bridged By Alkanoyl

Objective:In order to increase anticancer activities of chrysin,a series of chrysin amino acid derivatives was designed and synthesized with chrysin as raw materials,and their anticancer activities was evaculated with tumor cells in vitro.It was expected to obtain high efficiency,low toxicity,and good targeting anticancer drugs,which would be a foundation for the development of new anticancer drugs.Methods:The basic methods of drug synthesis including alkylation,hydrolysis and amide condensation were used to modify the hydroxyl groups at the C7 position of chrysin by the introduction of different amino acids,and eventually a series of chrysin derivatives was obtained.The antiproliferation activity of human hepatocellular carcinoma cell line HepG2 and human breast cancer MCF-7 were detected by the MTT assay.The apoptosis activity of Human Hepatocellular Carcinoma HepG2 and Human Breast Cancer MCF-7 which were induced by some active compounds were evaluated by flow cytometry(FCM).Rescults:In this paper,20 chrysin derivatives were synthesized and charactered by 'H NMR and 13C NMR,in which 18 compounds were not reported in the literature before.The MTT assay in vitro showed that most compounds had the stronger antiproliferation activity of human hepatoma cell line HepG2 and human breast cancer cell line MCF-7 in comparison with the parent compound chrysin.The proliferation activity of compounds 12 and 16 was stronger than 5-fluorouracil in HepG2.Compound 11 and 19 had the stronger proliferation effect of breast cancer MCF-7 cells than 5-fluorouracil.The results of flow cytometry revealed that compounds 16?19 could induce apoptosis of HepG2?MCF-7 in a dose-dependent manner.Conclusion:In this study,we successfully introduced alkanoyl at C7 position of chrysin.A series of chrysin amino acid derivatives bridged by alkanoyl was synthesized with high yields and mild conditions,which increase the study range of this kind of compounds.Cell experiments in vitro has preliminarily evaluated the role of these synthesized chrysin amino acid derivatives in inhibiting the proliferation of cancer cells and explored the possible mechanism of their anticancer effects,which could provide a reference for further development of new anticancer drugs in the future.