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有机化学
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有机化学 ›› 2020, Vol. 40 ›› Issue (1): 69-77.DOI: 10.6023/cjoc201907018 上一篇    下一篇

研究论文

新型丁烯内酯衍生物的设计合成及诱导胃癌细胞凋亡研究

徐海伟, 李媛媛, 董航歧, 孟夏, 赵玲洁, 吕春涛, 王振亚, 金成允   

  1. 郑州大学药学院 药物关键制备技术教育部重点实验室 新药创制与药物安全性评价河南省协同创新中心 药物质量控制与评价河南省重点实验室 郑州 450001
  • 收稿日期:2019-07-12 修回日期:2019-08-14 发布日期:2019-09-18
  • 通讯作者: 金成允, 王振亚 E-mail:cyjin@zzu.edu.cn;barton118@163.com
  • 基金资助:
    河南省自然科学基金（No.182300410367）和河南省高校科技创新人才（No.15HASTIT036）资助项目.

Design and Synthesis of Novel Butenolide Derivatives and Inducing Apoptosis in Gastric Cancer Cells

Xu Haiwei, Li Yuanyuan, Dong Hangqi, Meng Xia, Zhao Lingjie, Lü Chuntao, Wang Zhenya, Jin Chengyun   

  1. Key Laboratory of Drug Preparation Technologies, Ministry of Education, Key Laboratory of Henan Province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
  • Received:2019-07-12 Revised:2019-08-14 Published:2019-09-18
  • Supported by:
    Project supported by the Natural Science Foundation of Henan Province (No. 182300410367), and the Scientific Innovation Talent Award from the Department of Education of Henan Province (No. 15HASTIT036).

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开发了一条合成天然产物Uncinine的新方法，基于此设计合成了一系列新型的丁烯内酯衍生物.通过噻唑蓝（MTT）法评价了目标化合物对胃癌细胞的增殖抑制活性，分析了其构效关系.其中，3-吗啉甲基-4-（4-叔丁基苯基）亚基丁烯内酯（9l）对MGC803的IC50为2.9 μmol/L，对胃癌细胞MGC803、HGC27以及SGC7901具有明显的选择性增殖抑制作用，而对正常的胃粘膜上皮细胞GES1具有较小的毒性.初步的作用机制研究表明，化合物9l诱导胃癌细胞MGC803凋亡依赖Caspase 9/3激活.

关键词: 丁烯内酯, 合成, 胃癌,诱导凋亡, Caspase

A new method of preparation for natural product Uncinine was reported. According to the method, a series of novel butenolides derivatives were designed and synthesized based on the natural product Uncinine. Most of the synthetic compounds showed significant anti proliferation activity against MGC-803. Among of them, (Z)-5-(4-(tert-butyl)-benzylidene)-3-(morpholinomethyl)furan-2(5H)-one (9l) showed potent anticancer effect with IC50 of 2.9 μmol/L in gastric cancer cell MGC803 and showed good selectivity to gastric cancer cells MGC803, HGC27, SGC7901 and less cytotoxicity in normal gastric epithelial cell line (GES1). The research on the molecular level suggests that the mechanism of compound 9l inducing apoptosis in gastric cancer cells is partially dependent on activation of caspase-9/3.

Key words: butenolide, synthesis, gastric cancer, apoptosis, caspase