Synthesis and biological evaluation of 1-arylsulfonyl-5-(N -hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo

Mei Jung Lai, Han Li Huang, Shiow Lin Pan, Yi Min Liu, Chieh Yu Peng, Hsueh Yun Lee, Teng Kuang Yeh, Po Hsien Huang, Che Ming Teng, Ching Shih Chen, Hsun Yueh Chuang, Jing Ping Liou

研究成果: 雜誌貢獻文章

46 引文 (Scopus)

摘要

A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI 50 values ranging from 0.36 to 1.21 μM against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC 50 values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.
原文英語
頁(從 - 到)3777-3791
頁數15
期刊Journal of Medicinal Chemistry
55
發行號8
DOIs
出版狀態已發佈 - 四月 26 2012

指紋

Indoles
Histone Deacetylase Inhibitors
Heterografts
Isoenzymes
Cell Line
Lung
Neoplasms
Lead

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

引用此文

Synthesis and biological evaluation of 1-arylsulfonyl-5-(N -hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo. / Lai, Mei Jung; Huang, Han Li; Pan, Shiow Lin; Liu, Yi Min; Peng, Chieh Yu; Lee, Hsueh Yun; Yeh, Teng Kuang; Huang, Po Hsien; Teng, Che Ming; Chen, Ching Shih; Chuang, Hsun Yueh; Liou, Jing Ping.

於: Journal of Medicinal Chemistry, 卷 55, 編號 8, 26.04.2012, p. 3777-3791.

研究成果: 雜誌貢獻文章

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abstract = "A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI 50 values ranging from 0.36 to 1.21 μM against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC 50 values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.",
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AU - Lai, Mei Jung

AU - Huang, Han Li

AU - Pan, Shiow Lin

AU - Liu, Yi Min

AU - Peng, Chieh Yu

AU - Lee, Hsueh Yun

AU - Yeh, Teng Kuang

AU - Huang, Po Hsien

AU - Teng, Che Ming

AU - Chen, Ching Shih

AU - Chuang, Hsun Yueh

AU - Liou, Jing Ping

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AB - A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI 50 values ranging from 0.36 to 1.21 μM against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC 50 values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.

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