Pharmacological intervention with 5-lipoxygenase: new insights and novel compounds

Abstract

5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrienes (LTs) that exert a large number of different biological activities mediated by specific G-protein-coupled receptors. LTB₄ is a typical pro-inflammatory mediator that recruits and activates leukocytes, whereas the cysteinyl-containing LTC₄, D4 and E₄ cause vascular permeability and smooth muscle contraction. Recent studies have implicated LTs and also other 5-LO products in bone metabolism, and the cardiovascular system, as well as in proliferation and (tumour) cell survival. Therefore, pharmacological intervention with 5-LO product synthesis represents a reasonable strategy for the treatment of a number of disease states, including allergic and inflammatory disorders, atherosclerosis and other cardiovascular diseases, osteoporosis and certain types of cancer. This review summarises the pharmacological concepts in 5-LO inhibition and focuses on novel pharmacological approaches in the devel-opment of drugs designed to intervene with dis-eases related to 5-LO prod-ucts.

Keywords::

• 5-lipoxygenase
• arachidonic acid
• asthma
• inflammation
• inhibitor
• leukotriene