Identification of a potent and stable antiproliferative agent by the prodrug formation of a thiolate histone deacetylase inhibitor.
To identify prodrugs of a thiolate histone deacetylase inhibitor NCH-31 that show potent antiproliferative activity and are stable in human plasma, we synthesized several candidate prodrugs of NCH-31. Among these compounds, S-2-methyl-3-phenylpropanoyl compound 2 showed more potent antiproliferative activity and higher stability in human plasma than S-isobutyryl compound NCH-51.
Suzuki
Takayoshi
T
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
Hisakawa
Shinya
S
Itoh
Yukihiro
Y
Maruyama
Sakiko
S
Kurotaki
Mineko
M
Nakagawa
Hidehiko
H
Miyata
Naoki
N
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C519721:NCH-31 compound; D011355:Prodrugs; D013844:Thiazoles