Targeting Lipoxygenases (LOs): Drug Design And Discovery
Eleni Pontiki and Dimitra Hadjipavlou–Litina
Affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
Keywords: Lipoxygenase, leukotrienes, inflammation, asthma, arthritis, psoriasis, FLAP inhibitors.
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
In this review we will update the research efforts within the LOs inhibition and we will present recent findings, of LO inhibitors.
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