1‐Arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines Histone Deacetylase Inhibitors Are Potent Cytokine Release Suppressors |
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| Authors: | Dr Hsueh‐Yun Lee Dr Chia‐Ron Yang Dr Mei‐Jung Lai Han‐Li Huang Yi‐Ling Hsieh Yi‐Min Liu Dr Teng‐Kuang Yeh Yu‐Hsuan Li Samir Mehndiratta Dr Che‐Ming Teng Dr Jing‐Ping Liou |
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| Affiliation: | 1. School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031 (Taiwan);2. School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Section 1, Ren‐Ai Road, Taipei 10051 (Taiwan);3. Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Section 1, Ren‐Ai Road, Taipei 10051 (Taiwan);4. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053 (Taiwan) |
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| 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. |
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| Keywords: | anti‐inflammatory agents gene expression histone deacetylase indolines inhibitors |
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