2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase
Journal
European Journal of Medicinal Chemistry
Journal Volume
122
Pages
92-101
Date Issued
2016
Author(s)
Lee H.-Y.
Chang C.-Y.
Su C.-J.
Huang H.-L.
Mehndiratta S.
Chao Y.-H.
Hsu C.-M.
Kumar S.
Sung T.-Y.
Huang Y.-Z.
Li Y.-H.
Liou J.-P.
Abstract
This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.
SDGs
Type
journal article