有机化学 ›› 2022, Vol. 42 ›› Issue (6): 1863-1871.DOI: 10.6023/cjoc202112015 上一篇    下一篇

研究简报

新型哈尔碱衍生物的合成与体外抗肿瘤活性研究

胡冬燕a,b, 韩广田b, 李喜安b, 任华忠b, 岳李荣b, 郭力a,*(), 封家福b,*()   

  1. a 成都中医药大学药学院 中药资源系统研究与开发利用国家重点实验室 成都 611137
    b 乐山职业技术学院 四川乐山 614000
  • 收稿日期:2021-12-07 修回日期:2022-02-12 发布日期:2022-02-25
  • 通讯作者: 郭力, 封家福
  • 基金资助:
    四川省中医药管理局科技(2020JC0069); 乐山市科技计划(20SZD067); 乐山市科技计划(20NZD007); 乐山职业技术学院科研基金(KY2019015); 乐山职业技术学院科研基金(KY2019016)

Synthesis and Evaluation in vitro of Novel Harmine Derivatives as Anticancer Activity Agents

Dongyan Hua,b, Guangtian Hanb, Xi'an Lib, Huazhong Renb, Lirong Yueb, Li Guoa(), Jiafu Fengb()   

  1. a State Key Laboratory of Resources Systems Research and Development Utilization of Traditional Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137
    b Leshan Vocational & Technical College, Leshan, Sichuan 614000
  • Received:2021-12-07 Revised:2022-02-12 Published:2022-02-25
  • Contact: Li Guo, Jiafu Feng
  • Supported by:
    Sichuan Provincial Administration of Traditional Chinese Medicine Technology Plan(2020JC0069); Science and Technology Plan of Leshan(20SZD067); Science and Technology Plan of Leshan(20NZD007); Research Foundation of Leshan Vocational & Technical College(KY2019015); Research Foundation of Leshan Vocational & Technical College(KY2019016)

以哈尔碱为原料, 经过N9-甲基化、溴代、Suzuki偶联、脱Boc保护和酰胺化等步骤, 合成了一系列新型的6-位取代的哈尔碱衍生物, 目标化合物的结构经1H NMR、13C NMR和高分辨质谱(HRMS)确证. 采用3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-四唑(MTS)法测试了目标化合物对白血病细胞HL-60、肺癌细胞A549、肝癌细胞SMMC-7721、乳腺癌细胞MCF-7和结肠癌细胞SW-480的增殖抑制作用. 实验结果表明, 部分化合物具有较好的抗肿瘤活性, 其中最强效的为化合物3o, 对HL-60、A549和SMMC-7721细胞的半数抑制浓度IC50值分别为0.27, 0.44和0.048 μmol/L, 其活性强于阳性对照顺铂, 抗肝癌细胞SMMC-7721的活性强于对照紫杉醇.

关键词: 哈尔碱, 衍生化, 抗癌活性

A series of novel 6-substituted harmine derivatives were synthesized from harmine in five steps: N9-methylation, bromination, Suzuki coupling, N-Boc deprotection, and amidation reaction. The structures of target compounds were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra (HRMS). The in vitro antiproliferative activities were evaluated in a panel of cancer cell lines (HL-60, A549, SMMC-7721, MCF-7 and SW-480) via 3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The results indicated that some compounds had good to excellent activities, and especially the most potent compound was 3o, whose IC50 values were 0.27 (against HL-60), 0.44 (against A549) and 0.048 μmol/L (against SMMC-7721), better than positive control drugs cisplatin and taxol (against SMMC-7721).

Key words: harmine, derivatization, antitumor activity