2-Aroylquinoline-5,8-diones as potent anticancer agents displaying tubulin and heat shock protein 90 (HSP90) inhibition

Kunal Nepali, Sunil Kumar, Hsiang Ling Huang, Fei Chiao Kuo, Cheng Hsin Lee, Ching Chuan Kuo, Teng Kuang Yeh, Yu Hsuan Li, Jang Yang Chang, Jing Ping Liou, Hsueh Yun Lee

研究成果: 雜誌貢獻文章

6 引文 斯高帕斯(Scopus)

摘要

This study reports the synthesis of a series of 2-aroylquinoline-5,8-diones (11-23) on the basis of scaffold hopping. The presence of a methoxy group at C6 assists the highly regioselective incorporation with various amines, and simplifies the structural identification process. Among the synthetic compounds, 6-dimethylamino-2-(3,4,5-trimethoxybenzoyl)-quinoline-5,8-dione (12) and 7-pyrrolidin-1-yl-2-(3,4,5-trimethoxybenzoyl)-quinoline-5,8-dione (23) exhibit remarkable anti-proliferative activity against the cancer cell lines tested with mean IC50 values of 0.14 and 0.27 μM, respectively. Compound 23 showed moderate inhibitory activity against tubulin polymerization with an IC50 value of 5.9 μM. In a western blot analysis, 23 caused induction of HSP70 and degradation of Akt, revealing that it possesses HSP90 inhibitory activity.
原文英語
頁(從 - 到)716-723
頁數8
期刊Organic and Biomolecular Chemistry
14
發行號2
DOIs
出版狀態已發佈 - 2015

    指紋

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

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