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 (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

HSP90 Heat-Shock Proteins
Dione
Tubulin
Antineoplastic Agents
Inhibitory Concentration 50
shock
quinoline
proteins
heat
Scaffolds
Polymerization
Amines
Western Blotting
Cells
cultured cells
Cell Line
Degradation
induction
amines
polymerization

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

引用此文

2-Aroylquinoline-5,8-diones as potent anticancer agents displaying tubulin and heat shock protein 90 (HSP90) inhibition. / Nepali, Kunal; Kumar, Sunil; Huang, Hsiang Ling; Kuo, Fei Chiao; Lee, Cheng Hsin; Kuo, Ching Chuan; Yeh, Teng Kuang; Li, Yu Hsuan; Chang, Jang Yang; Liou, Jing Ping; Lee, Hsueh Yun.

於: Organic and Biomolecular Chemistry, 卷 14, 編號 2, 2015, p. 716-723.

研究成果: 雜誌貢獻文章

Nepali, Kunal ; Kumar, Sunil ; Huang, Hsiang Ling ; Kuo, Fei Chiao ; Lee, Cheng Hsin ; Kuo, Ching Chuan ; Yeh, Teng Kuang ; Li, Yu Hsuan ; Chang, Jang Yang ; Liou, Jing Ping ; Lee, Hsueh Yun. / 2-Aroylquinoline-5,8-diones as potent anticancer agents displaying tubulin and heat shock protein 90 (HSP90) inhibition. 於: Organic and Biomolecular Chemistry. 2015 ; 卷 14, 編號 2. 頁 716-723.
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abstract = "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.",
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AU - Kumar, Sunil

AU - Huang, Hsiang Ling

AU - Kuo, Fei Chiao

AU - Lee, Cheng Hsin

AU - Kuo, Ching Chuan

AU - Yeh, Teng Kuang

AU - Li, Yu Hsuan

AU - Chang, Jang Yang

AU - Liou, Jing Ping

AU - Lee, Hsueh Yun

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