Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors.
In vitro evaluations of the selectivity of COX inhibitors are based on a great variety of experimental protocols. As a result, data available on cyclooxygenase (COX)-1/COX-2/5- lipoxygenase (LOX) selectivity of COX inhibitors lack consistency. We, therefore, performed a systematic analysis of the COX-1/COX-2/5-LOX selectivity of 14 compounds with selective COX inhibitory activity (Coxibs). The compounds belonged to different structural classes and were analyzed employing the well-recognized whole-blood assay. 5-LOX activity was also tested on isolated human polymorphonuclear leukocytes. Among COX inhibitors, celecoxib and ML-3000 (licofelone) inhibited 5-LOX in human neutrophils at micromolar ranges. Surprisingly, ML-3000 had no effect on 5-LOX product synthesis in whole-blood assay. In addition, we could show that inhibition of COX pathways did not increase the transformation of arachidonic acid by the 5-LOX pathway.
Sud'ina
G F
GF
A.N. Belozersky Institute of Physico-Chemical Biology of the Moscow State University, Leninskie Gory, Building A, 199991 Moscow, Russian Federation. sudina@genebee.msu.ru
Pushkareva
M A
MA
Shephard
P
P
Klein
T
T
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001769:Blood / Q000187:drug effects; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology; D011897:Random Allocation; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D002722:Chlorobenzenes
D001094:Arachidonate 5-Lipoxygenase; D016718:Arachidonic Acid; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D011758:Pyrroles; D013449:Sulfonamides; C060893:MK-886; D002722:Chlorobenzenes; C088092:licofelone