Title:Indole-3-ethylsulfamoylphenylacrylamides with Potent Anti-proliferative and Anti-angiogenic Activities
Volume: 16
Issue: 7
Author(s): Samir Mehndiratta, Shiow-Lin Pan, Sunil Kumar and Jing-Ping Liou
Affiliation:
Keywords:
Histone, HDAC, cancer, angiogenesis, SAHA, indole, sulfonamide.
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.
