QUINAZOLINE DERIVATIVES SUPPRESS NITRIC-OXIDE PRODUCTION BY MACROPHAGES THROUGH INHIBITION OF NOS-II GENE-EXPRESSION

We have found three novel quinazolidine derivatives which inhibit the formation of nitrite dose-dependently in a murine macrophage cell line , RAW264.7. The decreased nitrite formation was due not to the inhibit ion of nitric oxide synthase activity but to suppression of NOS II mRN A and protein expression. In rat vascular smooth muscle cells (VSMC), however, these compounds rather enhanced NOS TI mRNA. These compounds also prevented LPS-stimulated heme oxygenase-l (HO-1) and cyclooxygena se-2 (COX-2) gene expression in RAW264.7 cells, but again not in VSMC. The three quinazolidine derivatives specifically inhibit gene express ion of NOS II, HO-1 and COX-2 only in macrophage cells, indicating tha t they are selective inhibitors of inducible gene expression in macrop hages.