Potent histone deacetylase inhibitors: N-hydroxybenzamides with antitumor activities.
The screening tests of N-hydroxybenzamides for their HDAC-inhibitory activities led to the discovery of the promising compounds with a 2-naphthylcarbonyl group and with a 1,4-biphenylcarbonyl group. These compounds were further modified to optimize their physico-chemical profile. As a result, the inhibitor with a 6-amino-2-naphthylcarbonyl was obtained, which showed not only promising growth inhibitions against a panel of tumor cells, but also an improved water solubility. It exhibited the maximal 185% of survival rate (%T/C) in a in vivo experiment with P388 cell-inoculated mice.
Maeda
Taishi
T
Department of Biotechnology, Faculty of Engineering, Kansai University, Suita, Osaka 564-8680, Japan.
Nagaoka
Yasuo
Y
Kuwajima
Hiroshi
H
Seno
Chieko
C
Maruyama
Sakiko
S
Kurotaki
Mineko
M
Uesato
Shinichi
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D051379:Mice; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors