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2020 , Vol. 40 >Issue 6: 1598 - 1607

DOI: https://doi.org/10.6023/cjoc201911028

研究论文

新型香豆素类衍生物的合成及抗肿瘤活性研究

  • 时蕾 ,
  • 李子秋 ,
  • 崔鑫鑫 ,
  • 朱挺 ,
  • 庞晓静 ,
  • 李龙辉 ,
  • 罗德福 ,
  • 刘方芳 ,
  • 赵冰玉 ,
  • 龙跃 ,
  • 张赛扬
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  • a 郑州大学化学学院 郑州 450001;
    b 郑州大学药学院 郑州 450001;
    c 郑州大学基础医学院 郑州 450001

收稿日期: 2019-11-23

  修回日期: 2020-01-15

  网络出版日期: 2020-04-09

基金资助

国家自然科学基金（Nos.81703541，81673322）和中国博士后科学基金（No.2018M632812）资助项目.

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Synthesis and Anticancer Activity of Novel Coumarin Derivatives

  • Shi Lei ,
  • Li Ziqiu ,
  • Cui Xinxin ,
  • Zhu Ting ,
  • Pang Xiaojing ,
  • Li Longhui ,
  • Luo Defu ,
  • Liu Fangfang ,
  • Zhao Bingyu ,
  • Long Yue ,
  • Zhang Saiyang
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  • a College of Chemistry, Zhengzhou University, Zhengzhou 450001;
    b School of Pharmaceutical Sciences, Zhengzhou 450001;
    c School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001

Received date: 2019-11-23

  Revised date: 2020-01-15

  Online published: 2020-04-09

Supported by

Project supported by the National Natural Sciences Foundations of China (Nos. 81703541, 81673322) and the China Postdoctoral Science Foundation (No. 2018M632812).

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摘要

为了寻找结构新颖、活性较好的抗肿瘤化合物，设计合成了19个未见文献报道的3，4，5-三甲氧基苯基香豆素类化合物，并用核磁共振（NMR）和高分辨质谱（HRMS）等方法对化合物结构进行表征.用四甲基偶氮唑盐（MTT）法评价了该类化合物对人前列腺癌细胞（PC-3）、人食管癌细胞（EC-109）和人胃癌细胞（MGC-803）三种肿瘤细胞的抑制活性.结果显示，N-苄基-2-（（4-甲基-2H-色烯-2-酮-7-基）氧基）-N-（3，4，5-三甲氧基苯基）乙酰胺（4a）和N-（（5-氯苯并[b]噻吩-3-基）甲基）-2-（（4-甲基-2H-色烯-2-酮-7-基）氧基）-N-（3，4，5-三甲氧基苯基）乙酰胺（4n）对三种肿瘤细胞的抑制活性优于阳性对照药5-氟尿嘧啶，其中化合物4n对人前列腺癌细胞（PC-3）的抑制活性最好，其IC50为4.18 μmol/L.

关键词： 香豆素; 抗肿瘤; 合成

本文引用格式

时蕾 , 李子秋 , 崔鑫鑫 , 朱挺 , 庞晓静 , 李龙辉 , 罗德福 , 刘方芳 , 赵冰玉 , 龙跃 , 张赛扬 . 新型香豆素类衍生物的合成及抗肿瘤活性研究[J]. 有机化学, 2020 , 40(6) : 1598 -1607 . DOI: 10.6023/cjoc201911028

Abstract

Nineteen novel 3,4,5-trimethoxyphenyl coumarin derivatives have been synthesized and evaluated for antitumor activity against three human cancer cell lines (EC-109, PC-3 and MGC-803). These chemical structures were well characterized by NMR and HRMS spectroscopic methods. N-Benzyl-2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)-N-(3,4,5-trimethoxy-phenyl)acetamide) (4a) and N-((5-chlorobenzo[b]thiophen-3-yl)methyl)-2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)-N-(3,4,5-trimethoxyphenyl)acetamide) (4n) had better inhibitory activity against three kinds of tumor cells than 5-fluorouracil. Compound 4n showed the most potent antitumor activity against PC-3 cells with an IC50 value of 4.18 μmol/L.

Key words： coumarin; anticancer; synthesis

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