1-Arylsulfonyl-5-(N-hydroxyacrylamide)indolines Histone Deacetylase Inhibitors Are Potent Cytokine Release Suppressors

Hsueh Yun Lee, Chia-Ron Yang, Mei-Jung Lai, Han-Li Huang, Yi-Ling Hsieh, Yi-Min Liu, Teng-Kuang Yeh, Yu-Hsuan Li, Samir Mehndiratta, Che-Ming Teng, Jing Ping Liou

研究成果: 雜誌貢獻文章

12 引文 (Scopus)

摘要

A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines (7-15) has been developed; the compounds exhibited potent histone deacetylase (HDAC) inhibitory activities. Notably, almost all of this series exhibited better HDAC-inhibitory and antiproliferative activities than 3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide (6), as reported in a previous study. Among these compounds, 3-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-5-yl]-N-hydroxyacrylamide (9) showed a two- to tenfold increase in activity compared to SAHA (1) in the suppression of lipopolysaccharide-induced cytokine production. Compound 9 also caused a marked reduction in carrageenan-induced acute inflammation in a rat model. Taken together, these data indicated that 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines HDAC inhibitors exhibit potent anti-inflammatory activity. HDAC inhibitors suppress cytokine in vitro and in vivo: A panel of HDAC inhibitors was developed and evaluated for anti-inflammatory activity, which has not been well studied previously. Compound 1 was more potent than SAHA in vitro and in vivo. Our results suggest that 1 is a novel agent for the treatment of inflammation-associated diseases.

原文英語
頁(從 - 到)1248-1254
頁數7
期刊ChemBioChem
14
發行號10
DOIs
出版狀態已發佈 - 七月 2013

指紋

Histone Deacetylase Inhibitors
Histone Deacetylases
Cytokines
Anti-Inflammatory Agents
Inflammation
Carrageenan
Lipopolysaccharides
Rats
indoline
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology

引用此文

1-Arylsulfonyl-5-(N-hydroxyacrylamide)indolines Histone Deacetylase Inhibitors Are Potent Cytokine Release Suppressors. / Lee, Hsueh Yun; Yang, Chia-Ron; Lai, Mei-Jung; Huang, Han-Li; Hsieh, Yi-Ling; Liu, Yi-Min; Yeh, Teng-Kuang; Li, Yu-Hsuan; Mehndiratta, Samir; Teng, Che-Ming; Liou, Jing Ping.

於: ChemBioChem, 卷 14, 編號 10, 07.2013, p. 1248-1254.

研究成果: 雜誌貢獻文章

Lee, Hsueh Yun ; Yang, Chia-Ron ; Lai, Mei-Jung ; Huang, Han-Li ; Hsieh, Yi-Ling ; Liu, Yi-Min ; Yeh, Teng-Kuang ; Li, Yu-Hsuan ; Mehndiratta, Samir ; Teng, Che-Ming ; Liou, Jing Ping. / 1-Arylsulfonyl-5-(N-hydroxyacrylamide)indolines Histone Deacetylase Inhibitors Are Potent Cytokine Release Suppressors. 於: ChemBioChem. 2013 ; 卷 14, 編號 10. 頁 1248-1254.
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AU - Huang, Han-Li

AU - Hsieh, Yi-Ling

AU - Liu, Yi-Min

AU - Yeh, Teng-Kuang

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AB - A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines (7-15) has been developed; the compounds exhibited potent histone deacetylase (HDAC) inhibitory activities. Notably, almost all of this series exhibited better HDAC-inhibitory and antiproliferative activities than 3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide (6), as reported in a previous study. Among these compounds, 3-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-5-yl]-N-hydroxyacrylamide (9) showed a two- to tenfold increase in activity compared to SAHA (1) in the suppression of lipopolysaccharide-induced cytokine production. Compound 9 also caused a marked reduction in carrageenan-induced acute inflammation in a rat model. Taken together, these data indicated that 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines HDAC inhibitors exhibit potent anti-inflammatory activity. HDAC inhibitors suppress cytokine in vitro and in vivo: A panel of HDAC inhibitors was developed and evaluated for anti-inflammatory activity, which has not been well studied previously. Compound 1 was more potent than SAHA in vitro and in vivo. Our results suggest that 1 is a novel agent for the treatment of inflammation-associated diseases.

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