Reduction of the active-site iron by potent inhibitors of lipoxygenases.

摘要: Lipoxygenases are non-heme iron dioxygenases that catalyze the oxygenation of polyunsaturated fatty acids. Using soybean lipoxygenase-1 as a model, we have shown two classes lipoxygenase inhibitors currently in development potential antiinflammatory agents obtain significant amount their potency by reducing active-site from active ferric state to inactive ferrous state. It is not surprising members first these classes, 2-benzyl-1-naphthols, agents. The second class, N-alkyl-hydroxamic acids, were anticipated be sufficiently strong oxidized center; they provides additional evidence for having high reduction potential. This brings (at least) five number capable ion and suggests generality this approach rational design inhibitors.