Eleni Pontiki and Dimitra Hadjipavlou–Litina Pages 89 - 105 ( 17 )
Lipoxygenases (LOs) include several members and constitute a family of dioxygenases containing one nonheme iron atom per molecule, which oscillates between Fe2+ (inactive enzyme) and Fe3+ (active form) during the catalytic cycle. They catalyze the oxygenation of polyunsaturated fatty acids containing a (1Z, 4Z)-penta-1, 4-diene system to the corresponding hydroxyperoxy derivatives.
Although the cyclooxygenases could be considered specialized in the arachidonate pathway, the detailed mechanism of the LO reaction still remains controversial.
It has been found that LOs are implicated in several processes such as cell differentiation, inflammation and carcinogenesis. Development of drugs that interfere with the formation or effects of these metabolites would be important for the treatment of various diseases like asthma, psoriasis, ulcerative colitis, rheumatoid arthritis, atherosclerosis, cancer and blood vessel disorders. Till now, asthma consists of the only pathological case in which improvement has been shown by LO inhibitors. Thus, the research has been directed towards the development of drugs that interfere with the formation of leukotrienes.
In this review we will update the research efforts within the LOs inhibition and we will present recent findings, of LO inhibitors.
Lipoxygenase, leukotrienes, inflammation, asthma, arthritis, psoriasis, FLAP inhibitors.
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.