摘要
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 the flavonoid compound Davidigenin （dihydro-isoliquiritigenin, DH ILG）, and to study the anti-hepatocancer activity in vitro. Methods The hydroxyl group of 2,4-di hydroxyacetophenone and hydroxybenzaldehyde were protected selectively; and the chalcone isoliquiritigenin （ILG） was obtained by aldolization and deprotection reactions; and then, davidigenin was obtained within two types of catalytic hydrogenation; the chemical structure was identified by routine methods; human hepatoma cell lines Bel-7402 was used as an in vitro model for testing the anticancer activity within MTT method. Results The target compound yield obtained by two different catalytic hydrogenation reagents were 20% and 91.45%; Davidigenin showed significant inhibitory activity to the proliferation of hu man hepatoma Bel-7402 cells, with the potency below isoliquiritigenin. Conclusion The effect of selective reduction by platinum dioxide to α, β-unsaturated double bond of ILG was higher than those of palladium carbon catalytic reduction; human Bel-7402 hepatocarcinoma cells have a relatively high sensitivity to the anticancer mechanism of davidigenin; the α, β-unsaturated double bond in chalcone structure was essential for their anticancer activity. These results may have important role for the structure-activity relationship study of licorice chalcone compounds and for screening new anticancer drug candidate.
出处
《新疆医科大学学报》
CAS
2013年第2期150-155,共6页
Journal of Xinjiang Medical University
基金
国家自然科学基金(30960461)
