Molecules (Apr 2015)

5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors

  • Pu Xiang,
  • Hui Jie,
  • Yang Zhou,
  • Bo Yang,
  • Hui-Juan Wang,
  • Jing Hu,
  • Jian Hu,
  • Sheng-Yong Yang,
  • Ying-Lan Zhao

DOI
https://doi.org/10.3390/molecules20057620
Journal volume & issue
Vol. 20, no. 5
pp. 7620 – 7636

Abstract

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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.

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