新型含2-氨基-4-苯基噻唑结构的c-Met抑制剂设计合成及抗肿瘤活性研究
收稿日期: 2018-03-25
修回日期: 2018-06-06
网络出版日期: 2018-06-15
基金资助
国家自然科学青年基金(No.201601075)、辽宁省自然科学基金(No.2015020249)和辽宁省教育厅高校基本科研(No.JQL201715410)资助项目.
Design, Synthesis, and Biological Evaluation of Novel 2-Amino-4-phenylthiazole Derivatives as c-Met Inhibitors
Received date: 2018-03-25
Revised date: 2018-06-06
Online published: 2018-06-15
Supported by
Project supported by the National Natural Science Foundation for Young Scientists of China (No. 21601075), the Natural Science Foundation of Liaoning Province (No. 2015020249) and the General Research Projects of Liaoning Provincial Department of Education (No. JQL201715410).
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.
张志华 , 陈羽 , 吴红梅 , 崔博 , 熊武林 , 林腾辉 , 林荣南 , 郭宇 . 新型含2-氨基-4-苯基噻唑结构的c-Met抑制剂设计合成及抗肿瘤活性研究[J]. 有机化学, 2018 , 38(10) : 2648 -2656 . DOI: 10.6023/cjoc201803041
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.
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