18β-甘草次酸吡啶酰胺衍生物的定向合成及其初步抗癌活性研究

Rational Synthesis and Preliminary Anti-cancer Activities of 18β-Glycyrrhetinic Acid Derivatives Containing Pyridinecarboxamide

以18β-甘草次酸和2,5-吡啶二甲酸为起始原料,便捷地合成了5种含吡啶杂环多酰胺结构的18β-甘草次酸衍生物.全部新合成化合物的结构由1H NMR,13C NMR及HRMS等方法得到了确证.通过四甲基偶氮唑盐(MTT)法对所有新合成化合物的抑制人宫颈癌Hela细胞活性进行了体外评价,初步发现目标系列化合物对人宫颈癌Hela细胞均具有细胞毒活性,能够有效抑制Hela细胞增殖、诱导其凋亡,IC50最小值仅为0.02μmol·L-1,均优于临床抗肿瘤药物阿糖胞苷.

Five novel containing pyridinecarboxamide 18β-glycyrrhetinic acid derivatives have been designed and synthe- sized following the concept of ＇active structural splice＇. In vitro studies demonstrated that all derivatives showed strong an- ti-cancer activities in thiazolylblue （MTT） assay towards Hela cell lines. They were founded to inhibit the Hela cell lines pro- lifration and induce apoptosis as the lowest IC50 values was only 0.02 μmol·L^-1. Under the same conditions, these showed lower IC50 of cells growth than that of cytarabine. All findings supported further optimization efforts based on 18β-glycyrrhetinic acid as a lead compound to develop potential anti-cancer drug candidates.