Synthesis and cancer antiproliferative activity of new histone deacetylase inhibitors: hydrophilic hydroxamates and 2-aminobenzamide-containing derivatives.
New series histone deacetylase inhibitors comprising a hydroxamic acid or 2-aminobenzamide group as a zinc-chelating function were synthesized and evaluated for antiproliferative activities against a panel of human cancer cells. The 2-aminobenzamide series inhibitors generally had the potency in cell growth inhibitions comparable to that of MS-275. Among them, the compound having a (3,4-difluorobenzyl)(2-hydroxyethyl)amino group at one end and a 2-aminobenzamide group at the other of molecule showed the most promising profile as an anticancer drug candidate, since it had a comparatively low toxicity as did MS-275 against a normal fibroblast cell CCD-1059SK. Additionally, the derivative exhibited a high recovery in human plasma stability test.
Nagaoka
Y
Y
Department of Biotechnology, Faculty of Engineering, Kansai University, Suita, Osaka 564-8680, Japan.
Maeda
T
T
Kawai
Y
Y
Nakashima
D
D
Oikawa
T
T
Shimoke
K
K
Ikeuchi
T
T
Kuwajima
H
H
Uesato
S
S
D000970:Antineoplastic Agents / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D013055:Spectrophotometry, Infrared; D062367:ortho-Aminobenzoates / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D062367:ortho-Aminobenzoates; C000219:anthranilamide