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

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1248-1254
Number of pages7
JournalChemBioChem
Volume14
Issue number10
DOIs
Publication statusPublished - Jul 2013

Keywords

  • anti-inflammatory agents
  • gene expression
  • histone deacetylase
  • indolines
  • inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology

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