有机化学 ›› 2016, Vol. 36 ›› Issue (4): 795-802.DOI: 10.6023/cjoc201509002 上一篇    下一篇

研究论文

齐墩果酸和熊果酸衍生物的合成、表征及抗癌活性的研究

陈艳华a, 侯熙彦c, 支德福c, 李常a, 田甜a, 孙竞阳a, 赵龙铉a,b, 赵春晖b   

  1. a. 辽宁师范大学化学化工学院 大连 116029;
    b. 辽宁师范大学 生物技术与分子药物研发辽宁省重点实验室 大连 116029;
    c. 大连民族大学生命科学学院 大连 116600
  • 收稿日期:2015-09-01 修回日期:2015-10-30 发布日期:2015-12-15
  • 通讯作者: 赵龙铉, 赵春晖 E-mail:lxzhao@lnnu.edu.cn;zch@lnnu.edu.cn
  • 基金资助:

    国家自然科学基金(No.21101067)资助项目.

Synthesis, Characterization and Anticancer Activity of Oleanolic Acid and Ursolic Acid Derivatives

Chen Yanhuaa, Hou Xiyanc, Zhi Defuc, Li Changa, Tian Tiana, Sun Jingyanga, Zhao Longxuana,b, Zhao Chunhuib   

  1. a. School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
    b. Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029;
    c. College of Life Science, Dalian Nationalities University, Dalian 116600
  • Received:2015-09-01 Revised:2015-10-30 Published:2015-12-15
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21101067).

根据拼合原理,以天然产物齐墩果酸和熊果酸作为先导化合物,通过丁二酸连接片段,在C-28位分别导入哌嗪、N-甲基哌嗪及吗啉片段,共设计、合成了12种未见文献报道的齐墩果酸和熊果酸衍生物.利用IR、1H NMR、13C NMR和HRMS等波谱技术对所合成的目标化合物进行了结构表征,并采用3-(4,5-二甲基-2-噻唑)-2,5-二苯基溴化四氮唑噻唑蓝(MTT)法观察其对癌细胞的抑制作用,结果表明化合物OA-4OA-7OA-8aOA-8bUA-4UA-7UA-8aUA-8b对人乳腺癌细胞(MCF-7)、人宫颈癌细胞(Hela)和人肺腺癌细胞(A549)的抑制作用远优于先导化合物齐墩果酸和熊果酸,且OA-4,OA-7,UA-4UA-7与阳性对照物Gefitinib的IC50值相当.

关键词: 齐墩果酸, 熊果酸, 哌嗪, 抗癌活性

Based on the combination principle, twelve novel oleanolic acid and ursolic acid derivatives were designed and synthesized through introduction of piperazine, N-methyl piperazine and morpholine moiety in C-28 position. Structures of all target compounds were characterized by IR, 1H NMR, 13C NMR and HRMS. Their in vitro anticancer activities towards MCF-7, Hela and A549 cell lines were evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results indicate that OA-4, OA-7, OA-8a, OA-8b, UA-4, UA-7, UA-8a and UA-8b against MCF-7, Hela and A549 cells are obviously better than OA and UA, OA-4, OA-7, UA-4 and UA-7 are equally as well the IC50 of positive control gefitinib.

Key words: oleanolic acid, ursolic acid, piperazine, anticancer activity