|

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.

Cell Proliferation , Drug Design , Enhancer of Zeste Homolog 2 Protein , Quinolones , Humans , Quinolones/pharmacology , Quinolones/chemical synthesis , Quinolones/chemistry , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Enhancer of Zeste Homolog 2 Protein/metabolism , Structure-Activity Relationship , Cell Proliferation/drug effects , HeLa Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Drug Screening Assays, Antitumor , A549 Cells , Molecular Structure , Dose-Response Relationship, Drug , Cell Line, Tumor

: