New Trends in Dual 5-LOX / COX Inhibition

Xavier   de   Leval; Fabien      Julemont; Jacques      Delarge; Bernard      Pirotte; Jean-Michel      Dogne

doi:10.2174/0929867024606713

Abstract

Dual inhibitors are drugs able to block both the COX and the 5-LOX metabolic pathways. The interest of developing such compounds is supported by a large number of pharmacological studies. Compared to COX or LOX pathways single inhibitors, dual inhibitors present at least two major advantages. First, dual inhibitors, by acting on the two major arachidonic acid metabolic pathways, possess a wide range of antiinflammatory activity. Secondly, dual inhibitors appear to be almost exempt from gastric toxicity, which is the most troublesome side effect of COX inhibitors. The mechanism of their gastric-sparing properties is not completely understood, although it has been demonstrated that leukotrienes significantly contribute to the gastric epithelial injury. Finally, both COX and LOX derivatives (prostanoids and leukotrienes, respectively) are involved in other diseases than inflammation such as cancer proliferation where the use of dual inhibitors could be an interesting approach.

Keywords: cox inhibitors, prostanoids, leukotrienes, eicosanoids, cyclooxygenase, peroxidase, meclofenamic acid, flufenamic acid, mefenamic acid, niflumic acid