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

研究成果: 雜誌貢獻文章

26 引文 (Scopus)

摘要

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.

原文英語
頁(從 - 到)3623-3629
頁數7
期刊European Journal of Medicinal Chemistry
46
發行號9
DOIs
出版狀態已發佈 - 九月 2011

指紋

Indoles
Colchicine
Antineoplastic Agents
Multiple Drug Resistance
Tubulin
Microtubules
Binding Sites
Cells
Tissue
Cell Line
Pharmaceutical Preparations
Neoplasms
combretastatin A-1
fosbretabulin

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

引用此文

Synthesis and biological evaluation of 1-(4′-Indolyl and 6′-Quinolinyl) indoles as a new class of potent anticancer agents. / Lai, Mei-Jung; Chang, Jang-Yang; Lee, Hsueh Yun; Kuo, Ching-Chuan; Lin, Mei Hsiang; Hsieh, Hsing-Pang; Chang, Chi-Yen; Wu, Jian-Sung; Wu, Su-Ying; Shey, Kuang-Shing; Liou, Jing Ping.

於: European Journal of Medicinal Chemistry, 卷 46, 編號 9, 09.2011, p. 3623-3629.

研究成果: 雜誌貢獻文章

Lai, Mei-Jung ; Chang, Jang-Yang ; Lee, Hsueh Yun ; Kuo, Ching-Chuan ; Lin, Mei Hsiang ; Hsieh, Hsing-Pang ; Chang, Chi-Yen ; Wu, Jian-Sung ; Wu, Su-Ying ; Shey, Kuang-Shing ; Liou, Jing Ping. / Synthesis and biological evaluation of 1-(4′-Indolyl and 6′-Quinolinyl) indoles as a new class of potent anticancer agents. 於: European Journal of Medicinal Chemistry. 2011 ; 卷 46, 編號 9. 頁 3623-3629.
@article{d227b6c368224b1e83468f83d4154dc1,
title = "Synthesis and biological evaluation of 1-(4′-Indolyl and 6′-Quinolinyl) indoles as a new class of potent anticancer agents",
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}",
year = "2011",
month = "9",
doi = "10.1016/j.ejmech.2011.04.065",
language = "English",
volume = "46",
pages = "3623--3629",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
number = "9",

}

TY - JOUR

T1 - Synthesis and biological evaluation of 1-(4′-Indolyl and 6′-Quinolinyl) indoles as a new class of potent anticancer agents

AU - Lai, Mei-Jung

AU - Chang, Jang-Yang

AU - Lee, Hsueh Yun

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

PY - 2011/9

Y1 - 2011/9

N2 - 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.

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.

KW - Anti-mitotic agent

KW - Inhibition of tubulin polymerization

UR - http://www.scopus.com/inward/record.url?scp=80052932683&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052932683&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2011.04.065

DO - 10.1016/j.ejmech.2011.04.065

M3 - Article

C2 - 21641700

AN - SCOPUS:80052932683

VL - 46

SP - 3623

EP - 3629

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

IS - 9

ER -