Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs.
Dual COX/5-LOX (cyclooxygenase/5-lipoxygenase) inhibitors constitute a valuable alternative to classical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors for the treatment of inflammatory diseases. Indeed, these latter present diverse side effects, which are reduced or absent in dual-acting agents. In this review, COX and 5-LOX pathways are first described in order to highlight the therapeutic interest of designing such compounds. Various structural families of dual inhibitors are illustrated.
Charlier
Caroline
C
Lab. de Chimie Moléculaire Structurale, Facultés Universitaires N.-D. de la Paix, Rue de Bruxelles 61, B-5000, Namur, Belgium. caroline.charlier@fundp.ac.be
Michaux
Catherine
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D008958:Models, Molecular; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C073135:tepoxalin