A selective inhibitor of arachidonate 5-lipoxygenase scavenging peroxide activator.
A novel compound termed YT-18 (2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperazinyl) methyl]-5-benzofuranamine) selectively inhibited 5-lipoxygenases of porcine leukocytes (IC50 value, 7.5 microM), human leukocytes (1.5 microM), and rat basophilic leukemia cells (14 microM), which are responsible for bioactive leukotriene synthesis. In contrast, the compound up to 1 mM had almost no effect on 12-lipoxygenases of leukocytes and platelets, 15-lipoxygenase, and cyclooxygenases-1 and -2. YT-18 also inhibited the leukotriene synthesis in intact rat basophilic leukemia cells. In the 5-lipoxygenase reaction, YT-18 caused a lag phase, thereby delaying the start of the reaction. The lag was abolished by the addition of 13-hydroperoxy-linoleic acid in a dose-dependent manner, and most (but not all) of the reduced 5-lipoxygenase activity was recovered.
Suzuki
H
H
Department of Biochemistry, Tokushima University School of Medicine, Japan.
Miyauchi
D
D
Yamamoto
S
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D010545:Peroxides / Q000378:metabolism*; D051381:Rats; D013552:Swine
D000975:Antioxidants; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D010545:Peroxides; D016718:Arachidonic Acid