Synthesis and 5-lipoxygenase inhibitory activities of eicosanoid compounds.
Ten eicosanoid compounds (3, 6, 9, 11, 12, 15, 18, 21, 23, and 25), methyl (6E,8Z,11Z,14Z)-5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE, 10), leukotriene A4 (26), and (5S,6E,8E,10E,12RS,14E)-5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid (5,12-diHETE, 27) were prepared and their inhibitory activities against the 5-lipoxygenase from guinea pig polymorphonuclear leukocytes (PMNL) were tested. 5,6-Methanoleukotriene A4 (18) was especially a potent and specific inhibitor of the 5-lipoxygenase without inhibiting the cyclooxygenase and the 12-lipoxygenase. Leukotriene A4, 5-HETE, and 5,12-diHETE also have inhibitory activities against the 5-lipoxygenase at micromolar concentrations, which can regulate the formation of slow-reacting substance of anaphylaxis intracellulary.
D000818:Animals; D001091:Arachidonate Lipoxygenases; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology; D055598:Chemical Phenomena; D002621:Chemistry; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids; D066298:In Vitro Techniques; D007962:Leukocytes / Q000201:enzymology; D017572:Leukotriene A4; D007975:Leukotriene B4 / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D017572:Leukotriene A4; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases