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

doi:10.1021/jm300197a

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

生物化學暨分子生物學研究所

研究成果: Article › 同行評審

66 引文斯高帕斯（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	English
頁（從 - 到）	3777-3791
頁數	15
期刊	Journal of Medicinal Chemistry
卷	55
發行號	8
DOIs	https://doi.org/10.1021/jm300197a
出版狀態	Published - 2012 4月 26

All Science Journal Classification (ASJC) codes

分子醫學
藥物發現

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Lai, M. J., Huang, H. L., Pan, S. L., Liu, Y. M., Peng, C. Y., Lee, H. Y., Yeh, T. K., Huang, P. H., Teng, C. M., Chen, C. S., Chuang, H. Y., & Liou, J. P. (2012). Synthesis and biological evaluation of 1-arylsulfonyl-5-(N -hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo. Journal of Medicinal Chemistry, 55(8), 3777-3791. https://doi.org/10.1021/jm300197a

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

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.",

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

year = "2012",

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doi = "10.1021/jm300197a",

language = "English",

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Lai, MJ, Huang, HL, Pan, SL, Liu, YM, Peng, CY, Lee, HY, Yeh, TK, Huang, PH, Teng, CM, Chen, CS, Chuang, HY & Liou, JP 2012, 'Synthesis and biological evaluation of 1-arylsulfonyl-5-(N -hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo', Journal of Medicinal Chemistry, 卷 55, 編號 8, 頁 3777-3791. https://doi.org/10.1021/jm300197a

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T1 - Synthesis and biological evaluation of 1-arylsulfonyl-5-(N -hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo

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

PY - 2012/4/26

Y1 - 2012/4/26

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

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