Synthesis and biological evaluation of 1-(4¡ä-Indolyl and 6¡ä-Quinolinyl) indoles as a new class of potent anticancer agents

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• 作者：Mei-Jung Lai^a ; ¹ ; Jang-Yang Chang^b ; ^d ; ¹ ; Hsueh-Yun Lee^a ; Ching-Chuan Kuo^b ; Mei-Hsiang Lin^a ; Hsing-Pang Hsieh^c ; Chi-Yen Chang^b ; Jian-Sung Wu^c ; Su-Ying Wu^c ; Kuang-Shing Shey^e ; Jing-Ping Liou^a ; ^{jpl@tmu.edu.tw}
• 关键词：Inhibition of tubulin polymerization ; Anti-mitotic agent
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：September, 2011
• 年：2011
• 卷：46
• 期：9
• 页码：3623-3629
• 全文大小：367 K

文摘

A novel series of the biheterocycles-based compounds with core structure distinguished from combretastatin A-4 (1) and colchicine (5) have been synthesized and evaluated as potent anti-mitotic agents. Compound 1-(4¡ä-Indolyl and 6¡ä-quinolinyl)-4,5,6-trimethoxyindoles 13 and 19 showed substantial anti-proliferative activity against various human cancer cell lines, regardless to the tissue origin and the expression of multiple-drug resistance MDR1, with a mean IC₅₀ value of 38 and 24?nM respectively. Compound 13 (IC₅₀?=?1.7?¦ÌM) also exhibited similar anti-tubulin activities to 1 (IC₅₀?=?1.8?¦ÌM) and displayed strong binding property to the colchicine binding site on the microtubules. Computational modeling analysis revealed that the binding mechanism of compound 13 is similar to that of CA4.