Human 5-lipoxygenase has long been considered a possible therapeutic target for inflammatory diseases. Asthma is the principle disease target, however numerous other diseases have been postulated in the literature as possible targets for 5-LOX inhibition, such as allergic rhinitis, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, atherosclerosis, ischemiareperfusion injury, atopic dermatitis and acne vulgaris. The role of 5-LOX in the latter disease, acne vulgaris, has been shown to be related to the production of sebum in the derma. 5-LOX has also been implicated in another skin disease, seborrheic dermatitis. The involvement of 5-LOX in dandruff is because many systemic and superficial fungal infections are associated with inflammation. Ketoconazole is a widely used anti-fungal agent that is currently utilized as an active ingredient in anti-dandruff shampoo and previously for a wide range of fungal infections. Its mode of action is by inhibiting fungal sterol 14a-demethylase during ergosterol biosynthesis, thus retarding fungal growth. However, it has been proposed that part of its effectiveness is due to its anti-inflammation activity, since it also weakly inhibits 5-LOX. The anti-inflammatory activity of ketoconazole has also been seen for itraconazole, a similar anti-fungal therapeutic, which suggests a common theme for effective dandruff agents, dual anti-fungal/anti-inflammatory targeting. Nevertheless, the potency for ketoconazole and itraconazole against 5-LOX is poor, with IC50 values greater than 50 mM for both molecules, which indicates a potential for improvement in their anti-inflammatory activity. Numerous inhibitors for 5-LOX have been reported, which can be generally classified into three categories, reductive, iron ligands and competitive/mixed inhibitors, however, only one compound has been approved as a drug, zileuton. Zileuton is a potent and selective 5-LOX inhibitor but its mode of action is unusual for a therapeutic. It contains an N-hydroxyurea moiety, which is proposed to chelate to the active enzyme��s ferric ion and reduce it to the inactive ferrous ion. In general, chelation/reduction is not considered a viable mode of inhibition for a therapeutic since metal chelation tends toward promiscuous behavior with other metalloproteins and reductive inhibitors can be chemically inactivated in the cell. Nevertheless, zileuton has been shown to not only be selective against 5-LOX but also efficacious in the cell, which presents this class of inhibitors as a viable chemotype for 5-LOX inhibition. Other chelative inhibitors, such as nordihydroguaiaretic acid are also reductive due to the facile nature of inner sphere electron reduction. NDGA contains a catechol moiety, which binds to the active site ferric ion, PCI-32765 reducing it to the ferrous ion, with the concomitant oxidation of the catechol ABT-199 moiety to the semiquinone. This reactivity has previously been seen with the metalloenzyme, catechol dioxygenase, whose catechol substrate is activated to the semiquinone by the active site ferric ion for oxidation by molecular oxygen.