329966-80-5Relevant academic research and scientific papers
Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates
Suzuki, Takayoshi,Nagano, Yuki,Kouketsu, Akiyasu,Matsuura, Azusa,Maruyama, Sakiko,Kurotaki, Mineko,Nakagawa, Hidehiko,Miyata, Naoki
, p. 1019 - 1032 (2005)
To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong activity, and its potency was comparable to that of SAHA. The cancer cell growth inhibitory activity was verified to be the result of histone hyperacetylation and subsequent induction of p21WAF1/CIP1 by Western blot analysis. Kinetical enzyme assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis within the cell interacts with the zinc ion in the active site of HDACs.
Synthesis, antiproliferation, and docking studies of N-phenyl-lipoamide and 8-mercapto-N-phenyloctanamide derivatives: Effects of C6 position thiol moiety
Zhang, Shi-Jie,Hu, Wei-Xiao
, p. 3312 - 3320 (2012/11/07)
Some N-phenyl lipoamide and 8-mercapto- N-phenyloctanamide derivatives were synthesized and their in vitro antiproliferative activity was evaluated. The experimental results indicated that 8-mercapto-N-phenyloctanamides might be good histone deacetylase inhibitors rather than N-phenyl lipoamides, who had thiol moiety at C6 position. To verify the antiproliferation data on structural basis, in silico docking studies of the representative compounds into the crystal structure of histone deacetylase- like protein using AutoDock 4.0 program were performed. Furthermore, sulfur acetylated 8-mercapto-Nphenyloctanamide improved its in vitro antiproliferative activity, probably due to the increasing of its cell membrane permeability. While the identification of enzymatic target of N-phenyl lipoamides with dithiolane is still ongoing. Springer Science+Business Media, LLC 2011.
Thiol-based SAHA analogues as potent histone deacetylase inhibitors
Suzuki, Takayoshi,Kouketsu, Akiyasu,Matsuura, Azusa,Kohara, Arihiro,Ninomiya, Shin-Ichi,Kohda, Kohfuku,Miyata, Naoki
, p. 3313 - 3317 (2007/10/03)
In order to find novel nonhydroxamate histone deacetylase (HDAC) inhibitors, a series of thiol-based compounds modeled after suberoylanilide hydroxamic acid (SAHA) was synthesized, and their inhibitory effect on HDACs was evaluated. Compound 6, in which t
