CX-659S: a novel diaminouracil derivative that has antioxidative and acute anti-inflammatory activities

• Published in: European journal of pharmacology Vol. 438; no. 3; pp. 189 - 196
• Main Authors: Goto, Yuso, Watanabe, Nobuo, Kogawa, Noriaki, Tsuchiya, Masami, Takahashi, Osamu, Uchi, Hiroshi, Furue, Masutaka, Hayashi, Hideya
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.03.2002; Elsevier
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidant; Antioxidants - pharmacology; Arachidonic Acid - toxicity; Ascorbic Acid - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chromans - pharmacology; Dose-Response Relationship, Drug; Ear - pathology; Edema - chemically induced; Edema - prevention & control; Hydroxyl radical; Lipid peroxidation; Lipid Peroxidation - drug effects; Male; Medical sciences; Mice; Mice, Inbred ICR; Oxidation-Reduction - drug effects; Peroxynitrite; Peroxynitrous Acid - metabolism; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Tetradecanoylphorbol Acetate - toxicity; Uracil - analogs & derivatives; Uracil - pharmacology; Uracil derivative; Lipid peroxidation; Peroxynitrite; Uracil derivative; Antioxidant; Hydroxyl radical; Short term; Oxygen; Rodentia; Antiinflammatory agent; Central nervous system; Lipids; In vitro; Radical scavenger; Biological activity; Antiallergic; Free radical; In vivo; Vertebrata; Mammalia; Mouse; Animal; Mechanism of action; Hydroxyl; Brain (vertebrata); Peroxidation
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01340-7

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(1 H,3 H)-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.