Design, synthesis and activity evaluation of quinolinone derivatives as EZH2 inhibitors

  • Bioorg Med Chem Lett. 2024 Jun 1:105:129726. doi: 10.1016/j.bmcl.2024.129726.
Jin Cai  1 ,  Haoyuan You  2 ,  Xintong Qin  2 ,  Yuhong Wang  2 ,  Wei Li  2
Affiliations
  • 1. School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China. Electronic address: [email protected].
  • 2. School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China.
PMID: 38580135 DOI: 10.1016/j.bmcl.2024.129726
Abstract

The enhancer of zeste homologue 2 (EZH2) is the core catalytic subunit of polycomb repressive complex 2, which catalyzes lysine 27 methylation of histone H3. Herein, a series of quinolinone derivatives were designed and synthesized based on the structure of Tazemetostat as the lead compound. Compound 9l (EZH2WT IC50 = 0.94 nM) showed stronger antiproliferative activity in HeLa cells than the lead compound. Moreover, compound 9e (EZH2WT IC50 = 1.01 nM) significantly inhibited the proliferation and induced Apoptosis in A549 cells.

Keywords
Anti-tumor; EZH2 inhibitor; PRC2; Quinolinone derivatives.
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