title: 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines histone deacetylase inhibitors are potent cytokine release suppressors.
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.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031 (Taiwan).
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.forename: Chia-Ron
authors.initials: CR
authors.lastname: Yang
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Huang
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Hsieh
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Li
authors.forename: Samir
authors.initials: S
authors.lastname: Mehndiratta
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Teng
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000178:Acrylamides; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D007211:Indoles
keywords: anti-inflammatory agents; gene expression; histone deacetylase; indolines; inhibitors