Studies on lipoxygenase inhibitors. II. KF8940 (2-n-heptyl-4-hydroxyquinoline-N-oxide), a potent and selective inhibitor of 5-lipoxygenase, produced by Pseudomonas methanica.
Pseudomonas methanica KY4634 was found to produce 5-lipoxygenase inhibitor designated KF8940, MY12-62a and MY12-62c. The inhibitors were purified by solvent extraction, silica gel column chromatography, reversed-phase low pressure liquid chromatography and crystallization. The chemical structures of KF8940, MY12-62a and MY12-62c were determined to be 2-n-heptyl-4-hydroxyquinoline-N-oxide, 2-n-heptyl-4-hydroxyquinoline and 3-n-heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-dione, respectively, on the basis of their physico-chemical properties. Among them, KF8940 was the most potent inhibitor. The compound inhibited 5-lipoxygenase of rat basophilic leukemia cells in a dose-dependent manner and the half maximal inhibitory concentration (IC50) was 1.5 X 10(-7) M. At this concentration, KF8940 did not inhibit bovine platelet 12-lipoxygenase and cyclooxygenase, and the IC50 values for these enzyme were 3.5 X 10(-5) M and 1.7 X 10(-4) M, respectively. The results indicated that KF8940 is a potent and selective inhibitor of 5-lipoxygenase. The IC50 value of MY12-62c for 5-lipoxygenase was 1.9 X 10(-5) M and that of MY12-62a was 1.9 X 10(-5) M.
D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002621:Chemistry; D016861:Cyclooxygenase Inhibitors; D006912:Hydroxyquinolines / Q000302:isolation & purification* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D011549:Pseudomonas / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D006912:Hydroxyquinolines; D016859:Lipoxygenase Inhibitors; C001333:2-(n-heptyl)-4-hydroxyquinoline N-oxide; C049991:MY 12-62c; C049990:MY 12-62a; D001091:Arachidonate Lipoxygenases