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2012 , Vol. 70 >Issue 07: 852 - 858

DOI: https://doi.org/10.6023/A1111051

研究论文

新型18β-甘草次酸氨基二硫代甲酸酯衍生物的合成及抗癌活性研究

  • 陈凑喜 ,
  • 李学强 ,
  • 李天才 ,
  • 周学章
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  • a 宁夏大学化学化工学院 银川 750021;
    b 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: 2011-11-05

  修回日期: 2012-01-31

  网络出版日期: 2012-02-14

基金资助

国家自然科学基金(No. 21062014)、教育部科学技术研究重点项目(No. 210237)、宁夏自然科学基金(No. NZ0606)和云南大学自然资源药物化学教育部重点实验室开放基金(No. 200902205)资助项目.

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Synthesis and Anti-tumor Activities of Novel 18β-Glycyrrhetinic Acid Derivatives Attaching Dithiocarbamate Units

  • Chen Couxi ,
  • Li Xueqiang ,
  • Li Tiancai ,
  • Zhou Xuezhang
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  • 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 date: 2011-11-05

  Revised date: 2012-01-31

  Online published: 2012-02-14

Supported by

Project supported by National Natural Science Foundation of China (No. 21062014), Key Project of Chinese Ministry of Education (No. 210237), Natural Science Foundation of Ningxia Province of China (No. NZ0606) and Key Laboratory of Medicinal Chemistry for Natural Resource, Yunnan University (No. 200902205) for financial support.

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摘要

以18β-甘草次酸为原料首先经简单酰胺化反应方便地得到18β-甘草次酸哌嗪, 再与二硫化碳、碳酸钾以及不同结构卤代烃“一锅煮”法快速、高效地合成了10 种含氨基二硫代甲酸酯结构的新型甘草次酸酰胺类衍生物, 通过IR, 1HNMR, 13C NMR 和HR-MS 对所有新化合物进行了结构确证; 并以四甲基偶氮唑盐比色法(MTT)法评价了该类化合物对人肝癌细胞株SMMC-7721 的细胞毒活性. 初步生物活性研究结果表明, 该类化合物具有明显的抑制人肝癌细胞增殖、诱导其凋亡的细胞毒活性, 给药72 h, 半抑制浓度IC50 最优值仅为14.42 μg/mL.

关键词： 18β-甘草次酸; 氨基二硫代甲酸酯; 合成; 抗癌活性

本文引用格式

陈凑喜 , 李学强 , 李天才 , 周学章 . 新型18β-甘草次酸氨基二硫代甲酸酯衍生物的合成及抗癌活性研究[J]. 化学学报, 2012 , 70(07) : 852 -858 . DOI: 10.6023/A1111051

Abstract

Ten new 18β-glycyrrhetinic acid derivatives with dithiocarbamate units were prepared by amidation of 18β-glycyrrhetinic acid and piperazine followed with one-pot condensation of the amide, CS2 and alkyl halides in the presence of potassium carbonate in CHCl3. The structures of all the new compounds were identified by NMR spectra, IR and HRMS technology. Anti-tumor activities of the 18β-glycyrrhetinic acid derivatives against human hepatoma SMMC-7721 cell lines were evaluated by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. They were found to inhibit the liver cancer cell proliferation and induce apoptosis as the lowest IC50 value was only 14.42 μg/mL.

Key words： 18β-glycyrrhetinic acid; dithiocarbamates; synthesis; anti-tumor activity

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