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2020 , Vol. 40 >Issue 3: 669 - 678

DOI: https://doi.org/10.6023/cjoc201909042

研究论文

胡椒基咪唑盐类化合物的合成及生物活性研究

  • 刘正芬 ,
  • 字玉金 ,
  • 张琳琳 ,
  • 方永晟 ,
  • 沈艳珍 ,
  • 李艳 ,
  • 羊晓东 ,
  • 张洪彬
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  • a 云南大学教育部自然资源药物化学重点实验室 昆明 650091;
    b 中国科学院昆明植物研究所 植物化学与西部植物资源持续利用国家重点实验室 昆明 650204

收稿日期: 2019-09-30

  修回日期: 2019-10-31

  网络出版日期: 2020-04-02

基金资助

长江学者和创新团队发展计划（No.IRT17R94）、国家自然科学基金（Nos.21662043，21572197，U1402227）、云南省高校科技创新团队支持计划资助项目.

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Synthesis and Cytotoxic Activity of Novel Hybrid Compounds between Piperonyl and Imidazolium Salts

  • Liu Zhengfen ,
  • Zi Yujin ,
  • Zhang Linlin ,
  • Fang Yongsheng ,
  • Shen Yanzhen ,
  • Li Yan ,
  • Yang Xiaodong ,
  • Zhang Hongbin
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  • a Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan University, Kunming 650091;
    b State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204

Received date: 2019-09-30

  Revised date: 2019-10-31

  Online published: 2020-04-02

Supported by

Project supported by the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT17R94), the National Natural Science Foundation of China (Nos. 21662043, 21572197, U1402227), and the Innovative Research Team (in Science and Technology) in University of Yunnan Province.

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摘要

从胡椒酸出发，通过还原、甲磺酸酯化、偶联和成盐四步反应合成了一系列新型的胡椒基咪唑盐类化合物，其结构经1H NMR，13C NMR，HRMS以及X射线单晶衍射确定.对合成的新化合物进行了体外抗肿瘤细胞毒活性筛选，结果表明，1-（（苯并[d][1，3]二氧杂环戊烯-5-基甲基）-3-（2-萘甲基））-5，6-二甲基-1H-苯并[d]咪唑-3-溴盐（30）具有显著的细胞毒活性，对HL-60、SMMC-7721、A-549、MCF-7和SW-480肿瘤细胞株的活性均优于顺铂（DDP），尤其对HL-60肿瘤细胞株表现出较好的选择性细胞毒活性，其IC50值约为顺铂的7.2倍.进一步研究表明，化合物30具有诱导SMMC-7721细胞株在细胞周期G0/G1期阻滞和细胞凋亡的作用.

关键词： 胡椒基; 咪唑盐; 分子杂合; 构效关系; 细胞毒活性

本文引用格式

刘正芬 , 字玉金 , 张琳琳 , 方永晟 , 沈艳珍 , 李艳 , 羊晓东 , 张洪彬 . 胡椒基咪唑盐类化合物的合成及生物活性研究[J]. 有机化学, 2020 , 40(3) : 669 -678 . DOI: 10.6023/cjoc201909042

Abstract

A series of novel hybrid compounds between piperonyl and imidazolium salts were prepared from tryptophol by four steps of reduction, mesylation, coupling and salt formation. Their structures were confirmed by 1H NMR, 13C NMR, HRMS and X-ray crystallographic analysis. These compounds were evaluated in vitro against a panel of human tumor cell lines. The results showed that 1-((benzo[d] [1,3]dioxol-5-ylmethyl)-3-(2-naphthylmethyl))-5,6-dimethyl-1H-benzo[d]imidazol-3-ium bromide (30) exhibited remarkable inhibitory activity selectively against HL-60, SMMC-7721, A-549, MCF-7 and SW480 cell lines compared with DDP. In particular, the compound was more selective to HL-60 cell lines with IC50 values 7.2-fold lower than DDP. Further studies showed that compound 30 has the effect of inducing SMMC-7721 cell line arrest and cell apoptosis in cell cycle G0/G1.

Key words： piperonyl; imidazolium salts; molecular hybridization; structure-activity relationship; cytotoxic activity

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