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.
Copyright © 2024. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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A549 Cells
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Proliferation* / drug effects
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Dose-Response Relationship, Drug
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Drug Design*
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Drug Screening Assays, Antitumor
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Enhancer of Zeste Homolog 2 Protein* / antagonists & inhibitors
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Enhancer of Zeste Homolog 2 Protein* / metabolism
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HeLa Cells
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Humans
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Molecular Structure
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Quinolones* / chemical synthesis
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Quinolones* / chemistry
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Quinolones* / pharmacology
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Structure-Activity Relationship
Substances
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Quinolones
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Enhancer of Zeste Homolog 2 Protein
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EZH2 protein, human
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Antineoplastic Agents