5-Amino-2-Aroylquinolines as Highly Potent Tubulin Polymerization Inhibitors

A series of aroylquinoline derivatives were synthesized and evaluated for anticancer activity. 5-Amino-6-methoxy-2-aroylquinoline 15 showed more potent antiproliferative activity (IC50 values ranging from 0.2 to 0.4 nM) as compared to 1a (combretastatin A-4) (IC50 = 1.9−835 nM) against various human...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2010-03, Vol.53 (5), p.2309-2313
Main Authors: Nien, Chih-Ying, Chen, Yun-Ching, Kuo, Ching-Chuan, Hsieh, Hsing-Pang, Chang, Chi-Yen, Wu, Jian-Sung, Wu, Su-Ying, Liou, Jing-Ping, Chang, Jang-Yang
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
Humans
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Mass Spectrometry
Quinolines - chemical synthesis
Quinolines - chemistry
Quinolines - pharmacology
Structure-Activity Relationship
Tubulin - physiology
Tubulin Modulators - chemical synthesis
Tubulin Modulators - chemistry
Tubulin Modulators - pharmacology
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Summary:A series of aroylquinoline derivatives were synthesized and evaluated for anticancer activity. 5-Amino-6-methoxy-2-aroylquinoline 15 showed more potent antiproliferative activity (IC50 values ranging from 0.2 to 0.4 nM) as compared to 1a (combretastatin A-4) (IC50 = 1.9−835 nM) against various human cancer cell lines and a MDR-resistant cancer cell line. Compound 15 (IC50 = 1.6 μM) exhibited more potent inhibition of tubulin polymerization than 1a (IC50 = 2.1 μM) and showed strong binding property to the colchicine binding site of microtubules.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm900685y