1‐Arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines Histone Deacetylase Inhibitors Are Potent Cytokine Release Suppressors. Issue 10 (20th June 2013)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Chembiochem. Volume 14:Issue 10(2013)
• Page Start: 1248
• Page End: 1254
• Publication Date: 2013-06-20
• Subjects: anti‐inflammatory agents -- gene expression -- histone deacetylase -- indolines -- inhibitors; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300201
• Languages: English
• ISSNs: 1439-4227

Abstract

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‐1 H ‐indol‐5‐yl)‐ N ‐hydroxyacrylamide (6 ), as reported in a previous study. Among these compounds, 3‐[1‐(4‐methoxybenzenesulfonyl)‐2, 3‐dihydro‐1 H ‐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. Abstract : 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.