Novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides as Histone Deacetylase Inhibitors and Antitumor Agents

Title:	Novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides as Histone Deacetylase Inhibitors and Antitumor Agents
Authors:	Do, T. M. Dung Phan, T. P. Dung Dao, T. K. Oanh Pham, T. Hai Le, T. T. Huong Vu, D. Loi Hahn, Huynggu Han, Byung W. Kim, Jisung Han, sang - Bae Nguyen, Hai Nam
Keywords:	Histone deacetylase (HDAC) inhibitors;hydroxamic acids;3-substituted-2-oxoindoline;propenamide
Issue Date:	2015
Publisher:	Bentham Science
Citation:	Do T. M. Dung, Phan T. P. Dung, Dao T. K. Oanh, et al. Novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides as Histone Deacetylase Inhibitors and Antitumor Agents. Medicinal Chemistry, 2015, 11
Abstract:	Histone deacetylases (HDAC) are currently a group of validated targets for anticancer drug discovery and development. In our research program to find novel small molecules targeting these enzymes, we designed and synthesized two series of 3-hydroxyimino-2-oxoindoline- and 3- methoxyimino-2-oxoindoline-based N-hydroxypropenamides (3a-g, 6a-g). The results show that these propenamides potently inhibited HDAC2 with IC50 values in sub-micromolar range, approximately 10-fold lower than that of SAHA (also known as suberoylanilohydroxamic acid). Evaluation of cytotoxicity of these compounds in three human cancer cell lines revealed that most of the synthesized compounds were up to 5-fold more cytotoxic than SAHA. Docking studies showed that the compounds bound to HDAC2 at the binding site with higher binding affinities compared to SAHA. Our present results demonstrate that these novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides are potential for further development as anticancer agents. - See more at: http://www.eurekaselect.com/132732/article#sthash.qiWRAX4y.dpuf
URI:	http://repository.vnu.edu.vn/handle/VNU_123/11334
ISSN:	1573-4064
Appears in Collections:	SMP - Papers / Tham luận HN-HT