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

Mei-Jung Lai; Jang-Yang Chang; Hsueh Yun Lee; Ching-Chuan Kuo; Mei Hsiang Lin; Hsing-Pang Hsieh; Chi-Yen Chang; Jian-Sung Wu; Su-Ying Wu; Kuang-Shing Shey; Jing Ping Liou

doi:10.1016/j.ejmech.2011.04.065

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

Mei-Jung Lai, Jang-Yang Chang, Hsueh Yun Lee, Ching-Chuan Kuo, Mei Hsiang Lin, Hsing-Pang Hsieh, Chi-Yen Chang, Jian-Sung Wu, Su-Ying Wu, Kuang-Shing Shey, Jing Ping Liou

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

Abstract

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′-Indolyl and 6′-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 IC ₅₀ value of 38 and 24 nM respectively. Compound 13 (IC ₅₀ = 1.7 μM) also exhibited similar anti-tubulin activities to 1 (IC ₅₀ = 1.8 μM) 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.

Original language	English
Pages (from-to)	3623-3629
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	46
Issue number	9
DOIs	https://doi.org/10.1016/j.ejmech.2011.04.065
Publication status	Published - Sept 2011

Keywords

Anti-mitotic agent
Inhibition of tubulin polymerization

ASJC Scopus subject areas

Drug Discovery
Organic Chemistry
Pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2011.04.065

Cite this

Lai, M-J., Chang, J-Y., Lee, H. Y., Kuo, C-C., Lin, M. H., Hsieh, H-P., Chang, C-Y., Wu, J-S., Wu, S-Y., Shey, K-S., & Liou, J. P. (2011). Synthesis and biological evaluation of 1-(4′-Indolyl and 6′-Quinolinyl) indoles as a new class of potent anticancer agents. European Journal of Medicinal Chemistry, 46(9), 3623-3629. https://doi.org/10.1016/j.ejmech.2011.04.065

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abstract = "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′-Indolyl and 6′-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 IC 50 value of 38 and 24 nM respectively. Compound 13 (IC 50 = 1.7 μM) also exhibited similar anti-tubulin activities to 1 (IC 50 = 1.8 μM) 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.",

keywords = "Anti-mitotic agent, Inhibition of tubulin polymerization",

author = "Mei-Jung Lai and Jang-Yang Chang and Lee, {Hsueh Yun} and Ching-Chuan Kuo and Lin, {Mei Hsiang} and Hsing-Pang Hsieh and Chi-Yen Chang and Jian-Sung Wu and Su-Ying Wu and Kuang-Shing Shey and Liou, {Jing Ping}",

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AU - Kuo, Ching-Chuan

AU - Lin, Mei Hsiang

AU - Hsieh, Hsing-Pang

AU - Chang, Chi-Yen

AU - Wu, Jian-Sung

AU - Wu, Su-Ying

AU - Shey, Kuang-Shing

AU - Liou, Jing Ping

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AB - 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′-Indolyl and 6′-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 IC 50 value of 38 and 24 nM respectively. Compound 13 (IC 50 = 1.7 μM) also exhibited similar anti-tubulin activities to 1 (IC 50 = 1.8 μM) 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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