Aspirin exerts its analgesic, antipyretic and anti-inflammatory actions by inhibiting the enzyme cyclooxygenase and thus preventing the formation and release of prostaglandins. The elucidation by John Vane of the mechanism of action of aspirin in 1971 was followed twenty years later by the discovery of a second cyclooxygenase enzyme, COX-2 and the rapid development of selective inhibitors of th...

A new series of peptide-like derivatives containing different aromatic amino acids andpossessing pharmacophores of COX-2 inhibitors as SO2Me or N3 attached to the para positionof an end phenyl ring was synthesized for evaluation as selective cyclooxygenase-2 (COX-2)inhibitors. The synthetic reactions were based on the solid phase peptide synthesis methodusing Wang resin. One of the analogues, i...

Activation of the gene for inducible cyclooxygenase (cyclooxygenase-2 [Cox-2], prostaglandin endoperoxide synthase) is an early response to injury in vascular smooth muscle cells. We used in vitro and in vivo models to demonstrate that activation of quiescent smooth muscle cells by mitogens leads to a rapid, short-term rise in mRNA for Cox-2, followed by synthesis of new Cox-2 enzyme protein an...

Kidney failure is the common end of hypertension and renal diseases. Several authors have suggested that vasodilatory prostaglandins participate in the hemodynamic mechanism responsible for the development of kidney failure. However, the mechanism by which prostaglandins are increased in renal disease is not clear. Recently, 2 isoforms of the enzyme responsible for prostaglandin synthesis, cycl...

A. Cyclooxygenase (COX) localization – COX I and COX II are located on the luminal faces of endoplasmic reticulum (ER) membranes, and on the intermembrane faces of the nuclear envelope (NE). (The bilaminar (double) NE is continuous with the ER.) In contrast to most integral membrane proteins, such as glucagon and epinephrine receptors and the LDL receptor, COX I and COX II do not pass through m...

To explore the role of cyclooxygenase (COX) in endothelial cell migration and angiogenesis, we have used two in vitro model systems involving coculture of endothelial cells with colon carcinoma cells. COX-2-overexpressing cells produce prostaglandins, proangiogenic factors, and stimulate both endothelial migration and tube formation, while control cells have little activity. The effect is inhib...

Nonsteroidal anti-inflammatory drugs (NSAIDs) act mainly via inhibition of prostaglandins synthesis by inhibition of cyclooxygenase (COX) isoenzymes (COX1 and COX 2). Selective COX-2 inhibitors which are also known as coxibs provide the main therapeutic effects of NSAIDs. Zarghi et al. reported 6-benzoyl-2-(4-(methylsulfonyl)phenyl)quinoline-4-carboxylic acid (AZGH 101) as a novel derivative of...