Indole-3-ethylsulfamoylphenylacrylamides: Potent histone deacetylase inhibitors with anti-inflammatory activity

Samir Mehndiratta, Yi Ling Hsieh, Yi Min Liu, Amber Weiching Wang, Hsueh Yun Lee, Lung Yu Liang, Sunil Kumar, Che Ming Teng, Chia Ron Yang, Jing Ping Liou

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

A series of 2-methyl-1H-indol-3-ethylsulfamoylphenylacrylamides based on LBH589-PXD101 core have been synthesized and evaluated for their histone deacetylase (HDAC) inhibitory and anti-inflammatory activity. In vitro, compounds 9-12 show 2.6-fold better HDAC inhibition and 3-fold better IL-6 suppression compared to LBH589·HCl (1·HCl). Furthermore, these compounds did not show apparent cell viability suppression on macrophages while in contrast, treatment with 1·HCl resulted in significant reduction in cell viability as demonstrated by an MTT assay. Repressed expression of iNOS, COX-2 and reduced phosphorylation of p65 revealed the inhibitory effect of these analogues on inflammatory mediator release which is related to inhibited NF-KB signals. (N-Hydroxy-3-{3-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}- acrylamide) (9), exhibited ability superior to that of 1·HCl, was able to reduce carrageenan-induced acute inflammation in an animal model. Compounds 9-12 have potential anti-inflammatory activity and compound 9 can serve as lead compound for further development.

Original languageEnglish
Pages (from-to)468-479
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume85
DOIs
Publication statusPublished - Oct 6 2014

Fingerprint

Histone Deacetylase Inhibitors
Histone Deacetylases
Cell Survival
Anti-Inflammatory Agents
Cells
Lead compounds
Phosphorylation
Acrylamide
Macrophages
Carrageenan
Interleukin-6
Assays
Animals
Animal Models
Inflammation
indole
panobinostat
belinostat
histone deacetylase 3
In Vitro Techniques

Keywords

  • Anti-inflammatory activity
  • Histone deacetylase inhibitors
  • Indole

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Cite this

Indole-3-ethylsulfamoylphenylacrylamides : Potent histone deacetylase inhibitors with anti-inflammatory activity. / Mehndiratta, Samir; Hsieh, Yi Ling; Liu, Yi Min; Wang, Amber Weiching; Lee, Hsueh Yun; Liang, Lung Yu; Kumar, Sunil; Teng, Che Ming; Yang, Chia Ron; Liou, Jing Ping.

In: European Journal of Medicinal Chemistry, Vol. 85, 06.10.2014, p. 468-479.

Research output: Contribution to journalArticle

Mehndiratta, Samir ; Hsieh, Yi Ling ; Liu, Yi Min ; Wang, Amber Weiching ; Lee, Hsueh Yun ; Liang, Lung Yu ; Kumar, Sunil ; Teng, Che Ming ; Yang, Chia Ron ; Liou, Jing Ping. / Indole-3-ethylsulfamoylphenylacrylamides : Potent histone deacetylase inhibitors with anti-inflammatory activity. In: European Journal of Medicinal Chemistry. 2014 ; Vol. 85. pp. 468-479.
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