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2020 , Vol. 40 >Issue 3: 731 - 739

DOI: https://doi.org/10.6023/cjoc201907052

研究论文

1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究

  • 鄢龙家 ,
  • 黎永良 ,
  • 邓明高 ,
  • 陈安超 ,
  • 杜志云 ,
  • 董长治 ,
  • 陈惠雄
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  • a 广东工业大学轻工化工学院 广州 510006;
    b 巴黎笛卡尔大学生物医学系 巴黎 75006;
    c 巴黎狄德罗大学 巴黎 75013

收稿日期: 2019-07-30

  修回日期: 2019-09-21

  网络出版日期: 2020-04-02

基金资助

国家自然科学基金（No.21672043）资助项目.

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Design, Synthesis and Biological Activities of Compounds Containing 1,3,4-Oxadiazole or 1,3,4-Thiadiazole

  • Yan Longjia ,
  • Li Yongliang ,
  • Deng Minggao ,
  • Chen Anchao ,
  • Du Zhiyun ,
  • Dong Changzhi ,
  • Chen Huixiong
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  • a Faculty of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou, 510006, China;
    b Biomédicale, Université Paris Descartes, 75006 Paris, France;
    c Université Paris Diderot, 75013 Paris, France

Received date: 2019-07-30

  Revised date: 2019-09-21

  Online published: 2020-04-02

Supported by

Project supported by the National Natural Science Foundation of China (No. 21672043).

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摘要

为了寻求新型抗肿瘤药物，设计并合成了一系列新型1，3，4-噁二唑和1，3，4-噻二唑衍生物，对这些化合物在人类四种癌细胞：B-16（皮肤黑色素瘤细胞）、PC-3（人前列腺癌细胞）、U87（人原发性胶质母细胞瘤细胞）和A549（人非小细胞肺癌细胞）进行抗肿瘤活性评价.结果显示部分化合物具有较好的抗肿瘤活性，尤其是5-{6-[4-（2-羟基乙基）哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1，3，4-噻二唑-2-羧酸（2-甲氧基苯基）酰胺（8b）和5-{6-[4-（2-羟基乙基）哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1，3，4-噻二唑-2-羧酸（4-甲氧基苯基）酰胺（8c），对四种癌细胞都显示出较高的抗肿瘤活性，其抑制活性均优于阳性对照达沙替尼.随后对这类化合物抑制肿瘤的可能靶点开展了进一步研究.

关键词： 1,3,4-噁二唑; 1,3,4-噻二唑; 抗肿瘤; Src抑制剂

本文引用格式

鄢龙家 , 黎永良 , 邓明高 , 陈安超 , 杜志云 , 董长治 , 陈惠雄 . 1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究[J]. 有机化学, 2020 , 40(3) : 731 -739 . DOI: 10.6023/cjoc201907052

Abstract

In order to find new anti-tumor drugs, a series of novel 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives were designed and synthesized. The target compounds were evaluated for antitumor activity in vitro on four human cancer cell lines including B-16 (skin melanoma cells), PC-3 (human prostate cancer cells), U87 (human primary glioblastoma cells) and A549 (human non-small cell lung cancer cells). The results displayed that some of the compounds had good activities, especially, 5-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(2-methoxyphenyl)-1,3,4-thiadiazole-2-carboxamide (8b) and 5-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(4-methoxyphenyl)-1,3,4-thiadiazole-2-carboxamide (8c) showed high antitumor activities against four cancer cell lines, which was better than dasatinib. These compounds were further studied for their possible target of tumor suppression.

Key words： 1,3,4-oxadiazole; 1,3,4-thiadiazole; anti-cancer; Src inhibitor

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