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

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6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)716-723
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume14
Issue number2
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

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