5-甲氧基喹啉衍生物作为一类新型EZH2抑制剂
5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors.
作者信息
Xiang Pu, Jie Hui, Zhou Yang, Yang Bo, Wang Hui-Juan, Hu Jing, Hu Jian, Yang Sheng-Yong, Zhao Ying-Lan
机构信息
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
出版信息
Molecules. 2015 Apr 27;20(5):7620-36. doi: 10.3390/molecules20057620.
A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displayed an IC50 value of 1.2 μM against EZH2, decreased global H3K27me3 level in cells and also showed good anti-viability activities against two tumor cell lines. Due to the low molecular weight and the fact that no quinoline derivative has been reported as an EZH2 inhibitor, this compound could serve as a lead compound for further optimization.
合成了一系列喹啉衍生物，并作为增强子同源物2（EZH2）抑制剂进行了生物学评价。构效关系（SAR）研究发现了5-甲氧基-2-(4-甲基-1,4-二氮杂环庚烷-1-基)-N-(1-甲基哌啶-4-基)喹啉-4-胺（5k），其对EZH2的IC50值为1.2 μM，可降低细胞中整体H3K27me3水平，并且对两种肿瘤细胞系也显示出良好的抗生存活性。由于该化合物分子量低且尚无喹啉衍生物作为EZH2抑制剂的报道，因此该化合物可作为进一步优化的先导化合物。
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