有机化学 ›› 2015, Vol. 35 ›› Issue (4): 835-842.DOI: 10.6023/cjoc201410013 上一篇    下一篇

研究论文

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

陈凑喜a,b, 魏梦雪a,b, 李学强a,b, 李天才a,b, 周学章c   

  1. a 宁夏大学化学化工学院 银川 750021;
    b 宁夏大学宁夏天然药物工程技术研究中心 银川 750021;
    c 宁夏大学西部特色生物资源保护与利用教育部重点实验室 银川 750021
  • 收稿日期:2014-10-09 修回日期:2014-12-07 发布日期:2014-12-23
  • 通讯作者: 李学强 E-mail:lixq@nxu.edu.cn
  • 基金资助:

    国家自然科学基金(Nos. 21462032, 21062014)、宁夏高等学校科学技术研究(No. NGY.2013171)和宁夏大学人才引进科研启动基金(No. 80020241)资助项目.

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

Chen Couxia,b, Wei Mengxuea,b, Li Xueqianga,b, Li Tiancaia,b, Zhou Xuezhangc   

  1. a School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021;
    b Ningxia Development Center of Natural Products and Medication, Yinchuan 750021;
    c Key Laboratory of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan 750021
  • Received:2014-10-09 Revised:2014-12-07 Published:2014-12-23
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21462032, 21062014), the University of Science and Technology Research Project in Nignxia Province (No. NGY.2013171) and the Research Starting Funds for Imported Talents, Ningxia University (No. 80020241).

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0.02 μmol·L-1,均优于临床抗肿瘤药物阿糖胞苷.

关键词: 18β-甘草次酸, 吡啶, 酰胺, 衍生物, 抗癌活性

Five novel containing pyridinecarboxamide 18β-glycyrrhetinic acid derivatives have been designed and synthesized following the concept of ‘active structural splice’. In vitro studies demonstrated that all derivatives showed strong anti-cancer activities in thiazolylblue (MTT) assay towards Hela cell lines. They were founded to inhibit the Hela cell lines prolifration 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.

Key words: 18β-glycyrrhetinic acid, pyridine, amide, derivative, anti-tumor activity