Furanylazaindoles: Potent anticancer agents in vitro and in vivo

Hsueh Yun Lee, Shiow Lin Pan, Min-Chieh Su, Yi-Min Liu, Ching-Chuan Kuo, Yi-Ting Chang, Jian-Sung Wu, Chih-Ying Nien, Samir Mehndiratta, Chi-Yen Chang, Su-Ying Wu, Mei-Jung Lai, Jang-Yang Chang, Jing Ping Liou

研究成果: 雜誌貢獻文章

30 引文 (Scopus)

摘要

Preliminary biological data on 7-anilino-6-azaindoles (8-11) suggested that hydrophobic substituents at C7 contribute to enhancement of antiproliferative activity. A novel series of 7-aryl-6-azaindole-1-benzenesulfonamides (12-22) were developed and showed improved cytotoxicity compared to ABT751 (5). The conversion of C7 phenyl rings into C7 heterocycles led to a remarkable improvement of antiproliferative activity. Among all the synthetic products, 7-(2-furanyl)-1-(4-methoxybenzenesulfonyl)-6-azaindole (21) exhibited the most potent anticancer activity against KB, HT29, MKN45, and H460 cancer cell lines with IC50 values of 21.1, 32.0, 27.5, and 40.0 nM, respectively. Bioassays indicated that 21 not only inhibits tubulin polymerization by binding to tubulin at the colchicine binding site but also arrests the cell cycle at the G2/M phase with slight arrest at the sub-G1 phase. Compound 21 also functions as a vascular disrupting agent and dose-dependently inhibits tumor growth without significant change of body weight in an HT29 xenograft mouse model. Taken together, compound 21 has potential for further development as a novel class of anticancer agents.
原文英語
頁(從 - 到)8008-8018
頁數11
期刊Journal of Medicinal Chemistry
56
發行號20
DOIs
出版狀態已發佈 - 2013

指紋

Tubulin
Antineoplastic Agents
Body Weight Changes
G2 Phase
Colchicine
G1 Phase
Cell Cycle Checkpoints
Heterografts
Polymerization
Biological Assay
Cell Division
Inhibitory Concentration 50
Blood Vessels
Neoplasms
Binding Sites
Cell Line
Growth
6-azaindole
In Vitro Techniques
7-(2-furanyl)-1-(4-methoxybenzenesulfonyl)-6-azaindole

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

引用此文

Furanylazaindoles : Potent anticancer agents in vitro and in vivo. / Lee, Hsueh Yun; Pan, Shiow Lin; Su, Min-Chieh; Liu, Yi-Min; Kuo, Ching-Chuan; Chang, Yi-Ting; Wu, Jian-Sung; Nien, Chih-Ying; Mehndiratta, Samir; Chang, Chi-Yen; Wu, Su-Ying; Lai, Mei-Jung; Chang, Jang-Yang; Liou, Jing Ping.

於: Journal of Medicinal Chemistry, 卷 56, 編號 20, 2013, p. 8008-8018.

研究成果: 雜誌貢獻文章

Lee, HY, Pan, SL, Su, M-C, Liu, Y-M, Kuo, C-C, Chang, Y-T, Wu, J-S, Nien, C-Y, Mehndiratta, S, Chang, C-Y, Wu, S-Y, Lai, M-J, Chang, J-Y & Liou, JP 2013, 'Furanylazaindoles: Potent anticancer agents in vitro and in vivo', Journal of Medicinal Chemistry, 卷 56, 編號 20, 頁 8008-8018. https://doi.org/10.1021/jm4011115
Lee, Hsueh Yun ; Pan, Shiow Lin ; Su, Min-Chieh ; Liu, Yi-Min ; Kuo, Ching-Chuan ; Chang, Yi-Ting ; Wu, Jian-Sung ; Nien, Chih-Ying ; Mehndiratta, Samir ; Chang, Chi-Yen ; Wu, Su-Ying ; Lai, Mei-Jung ; Chang, Jang-Yang ; Liou, Jing Ping. / Furanylazaindoles : Potent anticancer agents in vitro and in vivo. 於: Journal of Medicinal Chemistry. 2013 ; 卷 56, 編號 20. 頁 8008-8018.
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abstract = "Preliminary biological data on 7-anilino-6-azaindoles (8-11) suggested that hydrophobic substituents at C7 contribute to enhancement of antiproliferative activity. A novel series of 7-aryl-6-azaindole-1-benzenesulfonamides (12-22) were developed and showed improved cytotoxicity compared to ABT751 (5). The conversion of C7 phenyl rings into C7 heterocycles led to a remarkable improvement of antiproliferative activity. Among all the synthetic products, 7-(2-furanyl)-1-(4-methoxybenzenesulfonyl)-6-azaindole (21) exhibited the most potent anticancer activity against KB, HT29, MKN45, and H460 cancer cell lines with IC50 values of 21.1, 32.0, 27.5, and 40.0 nM, respectively. Bioassays indicated that 21 not only inhibits tubulin polymerization by binding to tubulin at the colchicine binding site but also arrests the cell cycle at the G2/M phase with slight arrest at the sub-G1 phase. Compound 21 also functions as a vascular disrupting agent and dose-dependently inhibits tumor growth without significant change of body weight in an HT29 xenograft mouse model. Taken together, compound 21 has potential for further development as a novel class of anticancer agents.",
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AU - Kuo, Ching-Chuan

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AU - Lai, Mei-Jung

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