Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors.
Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which the mercaptoacetamide group was replaced by (mercaptomethyl)fluoroalkene, and their HDAC inhibitory activity was evaluated. Subnanomolar inhibition was observed for all synthetic compounds.
Osada
Satoshi
S
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University, 1 Honjo, Saga 840-8502, Japan. osadas@cc.saga-u.ac.jp
Sano
Satoshi
S
Ueyama
Mariko
M
Chuman
Yoshiro
Y
Kodama
Hiroaki
H
Sakaguchi
Kazuyasu
K
D015195:Drug Design; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013853:Thioacetamide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D006845:Hydrocarbons, Fluorinated; D013853:Thioacetamide