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目的合成黄酮类化合物Davidigenin(二氢异甘草素,DH-ILG),并对体外抗肝癌活性进行研究。方法对2,4-二羟基苯乙酮和对羟基苯甲醛进行羟基的保护,并通过羟醛缩合反应后行脱保护而合成异甘草素(ILG);通过2种催化氢化反应系统对ILG进行还原而制备目标化合物Davidigenin,对于氢化还原试剂进行筛选,用光谱方法对结构进行鉴定;应用人肝癌Bel-7402细胞株为体外模型,用MTT法观察Davidigenin对人肝癌细胞增殖的抑制活性。结果经2种催化氢化还原试剂得到的目标化合物产率分别为20%及91.45%;Davidigenin对人肝癌Bel-7402细胞的增殖有抑制活性,在浓度为25～200μg/mL范围内,其抑制率为2.76%～65.27%,且活性强度低于异甘草素。结论利用二氧化铂对查尔酮类化合物分子侧链中的α-β不饱和双键进行选择性还原反应的效果明显高于钯碳催化还原;人肝癌Bel-7402细胞对Davidigenin的抗癌活性具有一定的敏感性;查尔酮类化合物分子侧链中的α-β不饱和双键是其抗癌活性的必要条件。本研究对甘草查尔酮类化合物的抗癌构效关系研究及抗肝癌候选药物筛选奠定一定基础。
Objective To synthesize flavonoids Davidigenin (dihydroisoliquiritigenin, DH-ILG) and study the anti-hepatoma activity in vitro. Methods The hydroxyl groups of 2,4-dihydroxyacetophenone and p-hydroxybenzaldehyde were protected and deprotected by aldol condensation to synthesize isoliquiritigenin (ILG). Two kinds of catalytic hydrogenation systems were used to treat ILG. The target compound Davidigenin was prepared by reduction, and the hydrogenation reagents were screened and the structure was identified by spectroscopic methods. The human hepatoma Bel-7402 cell strain was used as an in vitro model to observe the inhibitory activity of Davidigenin on the proliferation of human hepatoma cells by MTT assay. Results The yields of the target compounds obtained by the two kinds of catalytic hydrogenation reduction reagents were 20% and 91.45%, respectively. Davidigenin had inhibitory activity on the proliferation of human hepatoma Bel-7402 cells, and the inhibition rate was in the range of 25-200 μg/mL. It is 2.76% to 65.27% and its activity intensity is lower than that of isoliquiritigenin. Conclusion The effect of platinum dioxide on the selective reduction of α-β unsaturated double bonds in the side chains of chalcone compounds is significantly higher than that of palladium-carbon catalytic reduction; the anti-cancer activity of human hepatoma Bel-7402 cells on Davidigenin It has certain sensitivity; the α-β unsaturated double bond in the side chain of chalcone compounds is a necessary condition for its anticancer activity. This study lays a foundation for the study of the anti-cancer structure-activity relationship of licorice chalcones and screening of anti-cancer drug candidates.