摘要/Abstract

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


PDF全文下载地址:

点我下载PDF