Indole-3-ethylsulfamoylphenylacrylamides with Potent Anti-proliferative and Anti-angiogenic Activities

Author(s): Samir Mehndiratta, Shiow-Lin Pan, Sunil Kumar, Jing-Ping Liou.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 16 , Issue 7 , 2016

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

HDAC inhibition is emerging as a new strategy for cancer therapy. We previously reported that Nhydroxy- 3-{4-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide (9) demonstrated potent histone deacetylases (HDAC) inhibition and anti-inflammatory effects. This continuous study provides detailed structureactivity relationship (SAR) of novel indol-3-ethylsulfamoylphenylacrylamides as anti-cancer agents. These compounds are endowed with potent HDAC inhibitory activity, almost 2.5 folds to 42 folds better than suberanilohydroxamic acid (SAHA). Compounds 8, 10, 11 and 17 exhibited significant inhibitory effects on various cancer cell lines with GI50 values in the range of 0.02 to 0.35 μM which are 10-50 folds better than SAHA. In-vivo nude mice model indicated the anti-angiogenic potential of these acrylamides. This study has indicated the potential of 3-{4-[2-(1-Ethyl-2-methyl-1H-indol-3-yl)-ethyl-N-tert-butoxycarbonylsulfamoyl]-phenyl}-N-hydroxy-acrylamide (11, mean GI50 = 0.04 μM) as a lead molecule for further development as anti-cancer agent.

Keywords: Histone, HDAC, cancer, angiogenesis, SAHA, indole, sulfonamide.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 7
Year: 2016
Page: [907 - 913]
Pages: 7
DOI: 10.2174/1871520615666151013125221
Price: $58

Article Metrics

PDF: 25
HTML: 3
EPUB: 1
PRC: 1