摘要/Abstract

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
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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