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2020 , Vol. 40 >Issue 3: 794 - 800

DOI: https://doi.org/10.6023/cjoc201908012

研究简报

新型1,3-二取代酞嗪酮类衍生物的合成及抗肿瘤活性研究

  • 张路野 ,
  • 张洋 ,
  • 包崇男 ,
  • 杨鹏 ,
  • 李二冬 ,
  • 孟娅琪 ,
  • 崔飞 ,
  • 周蕊 ,
  • 黄诗雨 ,
  • 郑甲信 ,
  • 单丽红 ,
  • 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 省部共建食管癌防治国家重点实验室 郑州 450052;
    d 教育部药物制备关键技术重点实验室 郑州 450001

收稿日期: 2019-08-08

  修回日期: 2019-10-11

  网络出版日期: 2020-04-02

基金资助

国家自然科学基金（No.81430085）、河南省自然科学基金（No.182300410321）、省部共建食管癌防治国家重点实验室开放基金（No.K2020000X）资助项目.

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Synthesis and Antitumor Activity of Novel 1,3-Disubstituted Pyridazinone Derivatives

  • Zhang Luye ,
  • Zhang Yang ,
  • Bao Chongnan ,
  • Yang Peng ,
  • Li Erdong ,
  • Meng Yaqi ,
  • Cui Fei ,
  • Zhou Rui ,
  • Huang Shiyu ,
  • Zheng Jiaxin ,
  • Shan Lihong ,
  • Liu Hongmin ,
  • Zhang Qiurong
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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 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University y, Zhengzhou 450052;
    d Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001

Received date: 2019-08-08

  Revised date: 2019-10-11

  Online published: 2020-04-02

Supported by

Project supported by the National Natural Science Foundation of China (No. 81430085), the Natural Science Foundation of Henan Province (No. 182300410321), and the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (No. K2020000X).

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摘要

为了寻找高效低毒的抗肿瘤药物，设计并合成新型的1，3位取代酞嗪酮类化合物.采用噻唑蓝（MTT）法对目标化合物在MCF-7（人乳腺癌细胞）、PC-3（人前列腺癌细胞）、SW-620（人结肠癌细胞）和HGC-27（人胃癌细胞）四种人类癌细胞的抗增殖活性进行评价.结果显示大部分化合物具有较好的抗增殖活性.其中，2-（4-（4-溴苯基）-1-氧代酞嗪-2（1H）-基）-N-（2-氟苯基）乙酰胺（5g）对MCF-7细胞的抗增殖活性较好，IC50值为6.01 μmol/L，为抗肿瘤药物的研究提供了思路.

关键词： 酞嗪; 衍生物; 合成; 抗增殖活性

本文引用格式

张路野 , 张洋 , 包崇男 , 杨鹏 , 李二冬 , 孟娅琪 , 崔飞 , 周蕊 , 黄诗雨 , 郑甲信 , 单丽红 , 刘宏民 , 张秋荣 . 新型1,3-二取代酞嗪酮类衍生物的合成及抗肿瘤活性研究[J]. 有机化学, 2020 , 40(3) : 794 -800 . DOI: 10.6023/cjoc201908012

Abstract

In order to find more efficient and low toxicity antitumor drugs, a series of novel 1,3-disubstituted pyridazinone derivatives were synthesized and evaluated for their antiproliferative activities against four human cancer cell lines (MCF-7, PC-3, SW-620 and HGC-27) in vitro. The results showed that most compounds had good antiproliferative activities, especially 2-(4-(4-bromophenyl)-1-oxo-tolylazine-2(1H)-yl)-N-(2-fluorophenyl)acetamide (5g) exhibited better antiproliferative activities with IC50 value of 6.01 μmol/L. In a nutshell, this work provided clues to discover antitumor agent based on the quinazoline scaffold.

Key words： pyridazinederiv; ative; synthesis; antiproliferative activity

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