摘要/Abstract

基于克唑替尼的结构特征，设计、合成了两个系列未见文献报道的新型2-氨基-4-苯基噻唑类衍生物.采用噻唑蓝（MTT）法测试了目标化合物对A549、HT29、Hela、Karpas299的细胞增殖抑制活性.结果显示，部分化合物具有较好的肿瘤细胞抑制活性，其中N-（3-（2-氨基噻唑-4-基）苯基）-3-氯苯甲酰胺（3d）对HT29细胞的活性最好，IC₅₀值为4.42 μmol/L.采用Western blot考察目标化合物3d在HT29细胞中MET信号通路中相关蛋白表达的影响.另外，利用分子对接方法，对目标化合物进行了初步的构效关系讨论.
关键词: 噻唑衍生物, c-Met抑制剂, 合成, 构效关系
Two series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized based on the structural features of crizotinib. The cell proliferation inhibition efficacy was estimated against A549, HT29, Hela and Karpas299 cell lines. The results revealed that some target compounds exhibited strong or moderate proliferation inhibition efficacy against tumor cells. N-(3-(2-Aminothiazol-4-yl)phenyl)-3-chlorobenzamide (3d) displayed significant activity against HT29 cancer cell with IC₅₀ value of 4.42 μmol/L, and influence of this compound on the expression of related proteins in the MET signaling pathway in HT29 cells was investigated by Western blot. In addition, the preliminary structure-activity relationship (SAR) of the derivatives was rationalized by docking studies.
Key words: thiazole derivative, c-Met inhibitor, synthesis, structure-activity relationship


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