1 5-Lipoxygenase Inhibitors and their Anti-inflammatory Activities

Publisher Summary This chapter elaborates about 5-Lipoxygenase inhibitors and their anti-inflammatory activities. Oxidation of arachidonic acid in mammalian cells gives rise to a number of metabolites, collectively called eicosanoids, which are intimately involved in inflammation and other physiological and pathological processes. Prostaglandins (PGs) are the first members of this family to be identified and characterized, and are involved in inflammatory and pain responses. The clinically useful non-steroidal anti-inflammatory drugs (NSAIDs) of today are considered to act by inhibiting the enzyme cyclo-oxygenase (CO), which converts arachidonic acid to prostaglandins. A second major pathway of arachidonate metabolism has been characterized, in which arachidonic acid is converted to proinflammatory products called leukotrienes (LTs). The enzyme 5-lipoxygenase (5-LO) initiates this cascade. 5-LO catalyzes the stereospecific conversion of arachidonic acid to a 5-hydroperoxyeicosatetraenoic acid (5-HPETE). The enzyme contains non-heme iron in the active site, and the mechanism of the transformation probably involves an organoiron intermediate or a dienyl radical which is trapped by molecular oxygen to produce 5-hydroperoxyeicosatetraenoic acid.