Cyclooxygenase COX inhibition

Flurbiprofen is a cyclooxygenase (COX)-inhibiting non-steroidal anti-inflammatory drug (NSAID). The COX-inhibiting activity resides primarily in the (S)-enantiomer whereas the (R)-enantiomer has scarce COX activity. (R)-Flurbiprofen has been found to inhibit tumor growth in various animal models. In vitro experiments have shown that this effect is based on the induction of a cell cycle block and apoptosis [21]. 

P. N. P. Rao, E. E. Knaus (2008) Evolution of nonsteroidal anti-inflammatory drugs (NSAlDs) Cyclooxygenase (COX) inhibition and beyond. J. Pharm. Pharmaceut. Sci., 11, 81-110. http //en.wikipedia.org/wiki/Acetylsalicylic acid (last access February 25, 2014). http //nobelprize.org/nobel prizes/medicine/laureates/1982/vane.html (last access February 25, 2014). 

P. N. Praveen Rao and E. E. Knaus, Evolution of non-steroidal antiinflammatory drugs (NSAIDs) cyclooxygenase (COX) inhibition and beyond, J. Pharm Pharmacol. ScL, 2008, 11, 81s-110s. 

Compounds 111 having structural features of the dual cyclooxygenase (COX)/5-lipooxygenase (5-LO) inhibitor tepoxalin and the 5-LO inhibitor ABT-761 were prepared. Many of these hybrid compounds are potent COX and 5-LO inhibitors two compounds (111, r =McO, R = R" = R = H, R = NH2, R = Me and r = MeO, R = R = Me, R" = R = H, R = Cl) inhibited eicosanoid biosynthesis in an ex vivo assay, but neither improved on the main deficiency of tepoxalin, duration of 5-LO inhibitory activity (99BMCL979). Compounds 111 inhibit the production of arachidonic acid products associated with 5-lipoxygenase and cyclooxygenase and are useful in the treatment of inflammatory disorders (99USP5925769). 

NS AIDs Cyclooxygenases (COX-1, COX-2) l Prostaglandins l Thromboxanes l Sensitization of sensory neurons f Inhibition of spinal neurons Nonselective gastrointestinal ulcers, perforation, bleeding, renal impairment COX-2 thrombosis, myocardial infarction, stroke... 

NSAIDs inhibit cyclooxygenases (COX), the enzymes that catalyze the transformation of arachidonic acid (a ubiquitous cell component generated from phospholipids) to prostaglandins and thromboxanes. Two isoforms, COX-1 and COX-2, are constitutively expressed in peripheral tissues and in the central nervous... 

Aspirin, non-acetylated salicylates, and other NSAIDs have analgesic, antipyretic, and anti-inflammatory actions. These agents inhibit cyclooxygenase (COX-1 and COX-2) enzymes, thereby preventing prostaglandin synthesis, which results in reduced nociceptor sensitization and an increased pain threshold. NSAIDs are the preferred agents for mild to moderate pain in situations that are mediated by prostaglandins (e.g., rheumatoid... 

Hong CH, Sun KH, Jin O, Sun SK, Kyung AN, Sang KL. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J Ethnopharmacol 2002 83 153-159. 

NSAIDs are drugs related to acetyls alley lie acid which inhibit cyclooxygenase (COX), the enzyme in the synthesis of PGs and thromboxanes from arachidonic acid. There are two isoforms of cyclooxygenase, COX-1 and COX-2 [121].The former is constitutively expressed in blood vessels, stomach and kidney, while COX-2 is normally not present at these sites. It can,... 

Outlook Cyclooxygenase (COX) has two isozymes COX-1, a constitutive form present in stomach and kidney and COX-2, which is induced in inflammatory cells in response to appropriate stimuli. Presently available NSAIDs inhibit both isozymes. The search for COX-2-selective agents (Celecoxib, Ro-fecoxib) is intensifying because, in theory, these ought to be tolerated better. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat the signs and symptoms of inflammation, particularly arthritic pain. - It is mainly through the inhibition of cyclooxygenases (COXs), key enzymes in prostaglandin (PG) biosynthesis from arachidonic acid, that NSAIDs exert their anti-inflammatory effect. 

SMP-114 (licofelone) is a drug candidate for rheumatoid arthritis, currently in Phase II clinical trials (Figure 8.57). It inhibits all three of the major enzymes involved in the arachidonic acid pathway (5-LOX, COX-1, and COX-2), thereby preventing production of both leukotrienes and prostaglandins. This mode of action could therefore lead to a better tolerability than that of conventional cyclooxygenase (COX-1 and COX-2) inhibitors because of the shunt of arachidonic acid metabolism toward the production of proinflammatory leukotrienes, via 5-lipoxygenase (LOX). 

Ibuprofen works by inhibiting the enzyme cyclooxygenase (COX), which in turn interferes with the synthesis of prostaglandins. COX exists as several coenzyme forms that are similar in structure COX-1, COX-2, COX-3 ibuprofen is a nonselective inhibitor of both COX-1... 

Classically, inflammation is a protective reaction of the body in response to some physical, chemical, or microbial injury and insult of the cells. Acute inflammation, rapid onset and shorter duration, is considered as a healthy response. However, when inflammation continues for prolonged period of time, it becomes detrimental and may raise the first step of a chronic disease (Medzhitov, 2008). Arachidonic acid/COX and nuclear factor- (NF- ) are well known inflammatory pathways which induce production of inflammatory mediators such as prostaglandins, thromboxanes, leukotrienes, and cytokines. Most commonly accepted mechanism of anti-inflammation is inhibition of cyclooxygenase (COX) activity. There are two kinds of cyclooxygenases COX-1 is natural protective enzyme of intestinal mucosa while COX-2 is induced by tissue damage as an inflammatory mediator (Maroon et al., 2006). NF- is a recently identified... 

Berg, J., Fellier, H., Christoph, T., Grarup, J., Stimmeder, D. The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro, Inflamm. Res. 1999, 48, 369-79. 

Although the arylpropionic acids contain a stereogenic center they are generally marketed as racemic mixtures. The only exception is naproxen, which is marketed as its (S)-enantiomer. NSAIDs produce their antiinflammatory effects by inhibiting cyclooxygenase (COX), the enzyme which catalyzes the first transformation in the biosynthetic conversion of arachidonic acid to the 20 carbon prostaglandins. 

Inflammation is now recognized as a key process in atherogenesis [Libby, 2002]. The potential for dietary flavonoids to inhibit inflammatory activities is of particular interest. A potential anti-inflammatory feature of the flavonoids is the ability to inhibit the biosynthesis of eicosanoids. Selected phenolic acids and some flavonoids have been shown to inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) pathways [Nijveldt et al., 2001 Takano-Ishikawa et al., 2006], Epicatechin and related flavonoids have been shown to inhibit the synthesis of pro-inflammatory cytokines in vitro [Sanbongi et al., 1997], and plasma metabolites of catechin and quercetin inhibit the adhesion of monocytes to cultured endothelial cells [Koga and Meydani, 2001]. Silymarin has been shown to inhibit the production of inflammatory cytokines, such as interleukin-1, interferon-, and tumor necrosis factor-a (TNFa), from macrophages and T-cells [Matsuda et al., 2005], Some flavonoids can inhibit neutrophil... 

---