Antipsoriatic and proinflammatory action of anthralin. Implications for the role of oxygen radicals

Anthralin is among the most effective agents for the topical treatment of psoriasis. However, this drug causes unpleasant side-effects such as inflammation and staining of the nonaffected skin surrounding a psoriatic lesion. The biochemical basis for the induction of an inflammatory response in the skin and the antipsoriatic effectiveness are uncertain, although several cellular targets of anthralin action have been identified. Because no single mechanism is operative, the view was taken that all the effects exerted by anthralin are caused by its redox activity leading to the generation of anthralin free radicals and oxygen radicals. Clear relationships between oxygen-radical production by anthralin and biological response are evident with respect to chemical lesions in cellular macromolecules such as DNA, lipid membranes, and enzymes, indicating that these species account for the antipsoriatic and proinflammatory effects elicited by anthralin. This poses new challenges for the medicinal chemist and provides impetus for identifying novel compounds having potential for an improved therapeutic index.