Effects of some isoxazolpyrimidine derivatives on nitric oxide and eicosanoid biosynthesis

The inhibitory effect of some isoxazolpyrimidine derivatives on iNOS and CO X-2 endotoxin induction in mouse peritoneal macrophages has been studied. T hree of these compounds inhibited nitrite and PGE(2) accumulation in a conc entration dependent-manner at mu M range. None of these active compounds af fected iNOS, COX-2, COX-1 or PLA(2) activities, although some reduced iNOS or COX-2 expression. Besides, no effect was observed on human neutrophil in flammatory responses (LTB4 biosynthesis and superoxide or elastase release) . Active compounds were assayed by oral administration in the mouse air pou ch model, where they inhibited nitrite accumulation without affecting PGE2 levels or leukocyte migration. (C) 2000 Elsevier Science Inc.