Issue 2, 2016

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

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.

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

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
12 Oct 2015
Accepted
09 Nov 2015
First published
09 Nov 2015

Org. Biomol. Chem., 2016,14, 716-723

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

K. Nepali, S. Kumar, H. Huang, F. Kuo, C. Lee, C. Kuo, T. Yeh, Y. Li, J. Chang, J. Liou and H. Lee, Org. Biomol. Chem., 2016, 14, 716 DOI: 10.1039/C5OB02100F

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