CX-659S: a novel diaminouracil derivative that has antioxidative and acute anti-inflammatory activities.
We investigated the antioxidative activities and the effects on acute inflammation in mice of a novel diaminouracil derivative, CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione). CX-659S showed potent scavenging activities against the hydroxyl radical and peroxynitrite and inhibited lipid peroxidation in rat brain homogenates in vitro. Topically applied CX-659S dose-dependently inhibited arachidonic acid- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. Consistent with its antioxidative properties in vitro, CX-659S dramatically attenuated the accumulation of lipid peroxides in the mouse ear elicited by repeated application of TPA. Previously, we reported the effectiveness of CX-659S against contact hypersensitivity reactions in both mouse and guinea pig models. These present results further suggest the therapeutic potential of CX-659S for acute skin inflammation that may involve oxidative tissue damage.
Goto
Yuso
Y
Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation, 3-17-35, Niizo-Minami, Saitama 335-8502, Toda, Japan.
Watanabe
Nobuo
N
Kogawa
Noriaki
N
Tsuchiya
Masami
M
Takahashi
Osamu
O
Uchi
Hiroshi
H
Furue
Masutaka
M
Hayashi
Hideya
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000633:toxicity; D001205:Ascorbic Acid / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010084:Oxidation-Reduction / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002839:Chromans; D030421:Peroxynitrous Acid; D016718:Arachidonic Acid; D014498:Uracil; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C418807:CX 659S