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2022 , Vol. 42 >Issue 6: 1863 - 1871

DOI: https://doi.org/10.6023/cjoc202112015

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 ,
  • 韩广田 ,
  • 李喜安 ,
  • 任华忠 ,
  • 岳李荣 ,
  • 郭力 ,
  • 封家福
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  • 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

  网络出版日期: 2022-02-25

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)

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

  • Dongyan Hu ,
  • Guangtian Han ,
  • Xi'an Li ,
  • Huazhong Ren ,
  • Lirong Yue ,
  • Li Guo ,
  • Jiafu Feng
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  • 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
*E-mail: ;

Received date: 2021-12-07

  Revised date: 2022-02-12

  Online published: 2022-02-25

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)

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摘要

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

本文引用格式

胡冬燕 , 韩广田 , 李喜安 , 任华忠 , 岳李荣 , 郭力 , 封家福 . 新型哈尔碱衍生物的合成与体外抗肿瘤活性研究[J]. 有机化学, 2022 , 42(6) : 1863 -1871 . DOI: 10.6023/cjoc202112015

Abstract

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

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