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2019 , Vol. 39 >Issue 10: 2875 - 2881

DOI: https://doi.org/10.6023/cjoc201903062

研究论文

含脲砌块的4-氨基喹唑啉衍生物的设计、合成及抗肿瘤活性研究

  • 李二冬 ,
  • 孟娅琪 ,
  • 张路野 ,
  • 张洋 ,
  • 王继宽 ,
  • 张丹青 ,
  • 宋攀攀 ,
  • 辛景超 ,
  • 栗娜 ,
  • 郑甲信 ,
  • 可钰 ,
  • 刘宏民 ,
  • 张秋荣
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  • a 郑州大学药学院 郑州 450001
    b 新药创制与药物安全性评价河南省协同创新中心 郑州 450001
    c 河南省药物质量评价重点实验室 郑州 450001
    d 教育部药物制备关键技术重点实验室 郑州 450001

收稿日期: 2019-03-27

  修回日期: 2019-05-20

  网络出版日期: 2019-06-03

基金资助

国家自然科学基金(81430085);河南省自然科学基金(182300410321);河南省科技厅(No. 182102310249)

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Design, Synthesis and Antitumor Activity Evaluation of 4-Aminoquinazoline Derivatives Containing Urea Moiety

  • Erdong Li, ,
  • Yaqi Meng, ,
  • Luye Zhang, ,
  • Yang Zhang, ,
  • Jikuan Wang, ,
  • Danqing Zhang, ,
  • Panpan Song, ,
  • Jingchao Xin, ,
  • Na Li, ,
  • Jiaxin Zheng, ,
  • Yu Ke, ,
  • Hongmin Liu, ,
  • Qiurong Zhang,
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  • a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
    b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
    c Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou 450001
    d Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education, Zhengzhou 450001

Received date: 2019-03-27

  Revised date: 2019-05-20

  Online published: 2019-06-03

Supported by

Project supported by the National Natural Science Foundation of China(81430085);the Natural Science Foundation of Henan Province(182300410321);the Technology Department Project of Henan Province(No. 182102310249)

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摘要

为了寻找新的具有靶向治疗作用的抗肿瘤药物, 设计并合成了一系列新型的含脲砌块的4-氨基喹唑啉类衍生物, 并采用噻唑蓝(MTT)法测定目标化合物对MCF-7(人乳腺癌细胞)、MGC-803(人胃癌细胞)、SW620(人结肠癌细胞)、A549(人肺癌细胞)四种肿瘤细胞的抗肿瘤活性. 结果显示大部分化合物具有较好的抗肿瘤活性, 其中2-((4-((3,4,5-三甲氧基苯基)-氨基)喹唑啉-2-基)-硫代)-N-((3,4,5-三甲氧基苯基)氨基甲酰基)乙酰胺(10p)对MGC-803、SW620和A549三种细胞显示出最好的抗肿瘤活性, IC50值分别为(7.02±0.46)、(6.00±0.78)和(7.04±1.11) μmol?L –1, 其抗肿瘤活性和阳性对照品吉非替尼相当. 分子对接结果显示, 化合物10p能与EGFR很好地结合, 有可能成为潜在的抗肿瘤药物.

关键词： 脲砌块; 4-氨基喹唑啉; 合成; 抗肿瘤活性

本文引用格式

李二冬 , 孟娅琪 , 张路野 , 张洋 , 王继宽 , 张丹青 , 宋攀攀 , 辛景超 , 栗娜 , 郑甲信 , 可钰 , 刘宏民 , 张秋荣 . 含脲砌块的4-氨基喹唑啉衍生物的设计、合成及抗肿瘤活性研究[J]. 有机化学, 2019 , 39(10) : 2875 -2881 . DOI: 10.6023/cjoc201903062

Abstract

In order to find new anti-tumor drugs with targeted therapeutic effect, a series of novel 4-aminoquinazoline derivatives bearing urea moiety were designed, synthesized and evaluated for antitumor activity against four human cancer cell lines of MCF-7, MGC-803, SW620 and A549 using methyl thiazolyl tetrazolium (MTT) assay. Most of the target compounds exhibited excellent anti-tumor activity against the four human tumor cell lines. Among them, 2-((4-((3,4,5-trimethoxyphenyl)- amino)quinazolin-2-yl)-thio)-N-((3,4,5-trimethoxyphenyl)carbamoyl)acetamide (10p) showed the best antitumor activity against MGC-803, SW620 and A549 cancer cell lines with IC50 values of (7.02±0.46), (6.00±0.78) and (7.04±1.11) μmol? L –1, respectively. Its activity was comparable to the positive control of gefitinib. Molecular docking showed that compound 10p could bind well with EGFR, suggesting that it could be a potential antitumor agent.

Key words： urea moiety; 4-aminoquinazoline; synthesis; antitumor activity

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