Effects of some isoxazolpyrimidine derivatives on nitric oxide and eicosanoid biosynthesis.
The inhibitory effect of some isoxazolpyrimidine derivatives on iNOS and COX-2 endotoxin induction in mouse peritoneal macrophages has been studied. Three of these compounds inhibited nitrite and PGE2 accumulation in a concentration dependent-manner at microM range. None of these active compounds affected iNOS, COX-2, COX-1 or PLA2 activities, although some reduced iNOS or COX-2 expression. Besides, no effect was observed on human neutrophil inflammatory responses (LTB4 biosynthesis and superoxide or elastase release). Active compounds were assayed by oral administration in the mouse air pouch model, where they inhibited nitrite accumulation without affecting PGE2 levels or leukocyte migration.
Vidal
A
A
Department of Pharmacology, University of Valencia, Spain.
Ferrándiz
M L
ML
Ubeda
A
A
Guillén
I
I
Riguera
R
R
Quintela
J M
JM
Peinador
C
C
Moreira
M J
MJ
Alcaraz
M J
MJ
D000818:Animals; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008163:Luminescent Measurements; D008565:Membrane Proteins; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010080:Oxazoles / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D007527:Isoenzymes; D008565:Membrane Proteins; D010080:Oxazoles; D011743:Pyrimidines; D013481:Superoxides; D007975:Leukotriene B4; D009569:Nitric Oxide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D010741:Phospholipases A; D054467:Phospholipases A2; D010196:Pancreatic Elastase; D015232:Dinoprostone