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

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• 作者：Chih-Ying Nien ; Yun-Ching Chen ; Ching-Chuan Kuo ; Hsing-Pang Hsieh ; Chi-Yen Chang ; Jian-Sung Wu ; Su-Ying Wu ; Jing-Ping Liou ; Jang-Yang Chang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：March 11, 2010
• 年：2010
• 卷：53
• 期：5
• 页码：2309-2313
• 全文大小：780K
• 年卷期：v.53,no.5(March 11, 2010)
• ISSN：1520-4804

文摘

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.