Thiol-based SAHA analogues as potent histone deacetylase inhibitors.
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 the hydroxamic acid of SAHA was 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.
Suzuki
Takayoshi
T
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Aichi, Nagoya 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
Kouketsu
Akiyasu
A
Matsuura
Azusa
A
Kohara
Arihiro
A
Ninomiya
Shin-Ichi
S
Kohda
Kohfuku
K
Miyata
Naoki
N
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology; D000077337:Vorinostat
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013438:Sulfhydryl Compounds; D000077337:Vorinostat; D006655:Histone Deacetylases