15-Lipoxygenase inhibitors: A patent review

Abstract

Introduction: 15-Lipoxygenases (15-LOXes) are a family of iron-containingproteins that have the capability for unsaturated fatty acid peroxidation inanimals and plants. Two types of the enzyme, 15-LOX-1 and 15-LOX-2, havebeen recognized in mammals to have different abilities in the peroxidationof arachidonic acid and linoleic acid. In mammalians, the critical role of thementioned enzymes and their metabolites, hydroxyoctadecadienoic acid(HODE), lipoxins and eoxins, in the formation of inflammation, sensitivities,atherosclerosis and some cancers has been demonstrated.Areas covered: This article reviews relevant publications and patents on 15-LOX inhibitors from the points of view of synthesis and biological activities.Herein, based on the chemical structure and pharmacophore moiety, 15-LOXinhibitors are categorized into heterocyclic, phenolic, allyl and allyloxyderivatives.Expert opinion: It is noteworthy that to date no pharmaceutical productfrom 15-LOX inhibitors has been approved for therapeutic usage. Recently,the role of 15-LOX-1 in obesity, by directly relating 15-LOX-1 expression withthe proliferation and hypertrophy of adipose cells, has been reported. Basedon the role 15-LOX plays in promoting cancer by amplifying PPARγtranscrip-tion activity, however, it can be claimed that 15-LOX inhibitors will bedeemed suitable as chemotherapy agents in the near future