Novel 10-substituted antipsoriatic anthrones as inhibitors of epidermal 12-lipoxygenase and lipid peroxidation in membranes

Abstract

The ability of novel 10-substituted anthrones to inhibit 12-lipoxygenase (12-LO) in mouse epidermal homogenate and lipid peroxidation in both bovine brain phospholipid liposomes and erythrocyte ghosts was investigated, and compared with their ability to inhibit 5-lipoxygenase (5-LO) in bovine leukocytes. The compounds were fairly potent inhibitors of epidermal 12-LO, in addition to their strong inhibitory effects against leukocyte 5-LO. Although the antipsoriatic drug, anthralin, predominantly inhibited epidermal 12-LO, the novel derivatives were more selective 5-LO inhibitors. Compounds with free phenolic groups in the attached aromatic ring were also potent inhibitors of nonenzymatic lipid peroxidation in both sources of lipid substrate. This property was not correlated with their ability to inhibit the 5- and 12-LO pathways, suggesting that their mechanism of 5-/12-LO inhibition is not simply due to scavenging of peroxyl radicals generated at the active site of the enzymes. The compounds are dual-purpose inhibitors and may play a protective role against oxidative damage to psoriatic skin, in addition to their antiinflammatory 5-LO and 12-LO inhibitory properties.