Current Status and Recent Developments in Anthracenone Antipsoriatics

Klaus      Muller

doi:10.2174/1381612003400100

Abstract

Treatment of psoriasis is rapidly changing, and there have been dramatic additions such as topical vitamin D analogs and a topical retinoid to the therapeutic armamentarium in recent years. Even though drug therapy is often inadequate and serves only to abate the skin disorder, anthralin of the anthracenone antipsoriatics clears the rash totally. Of all antipsoriatic agents, anthralin has proven to be the most remarkably consistent and time-honored drug for treating the disease. However, anthralin therapy is accompanied by inflammation and staining of the nonaffected skin surrounding a psoriatic lesion. A large body of evidence has shown that the biochemical basis for its mechanism of action at the molecular level is related to its redox chemistry leading to the production of oxygen radicals. These can react with all classes of biological macromolecules and are involved in the principal cellular effects of the anthracenones. This article will focus on current strategies to minimize the potential of skin inflammation by anthralin and the underlying concepts of controlling and manipulating oxygen-radical generation which are essential for the rational design of novel anthracenones. Various studies have shown that by altering the structure of anthralin the in vitro profile can be markedly altered from an only moderate 5-lipoxygenase inhibitor to a more potent inhibitor of this enzyme, which may reflect improved activity against the inflammatory component of psoriasis while the antiproliferative activity is retained. The structural change is also accompanied by significantly diminished oxygen-radical generation and proinflammatory action on the skin. In particular, derivatives bearing a phenylacyl substituent in the critical 10-position of the anthracenone molecule have a favorable overall profile for achieving improved topical therapy of psoriasis.

Keywords: Anthracenone Antipsoriatics, Psoriasis, Streptococci, Stress, Endocrine factors, Beta blockers, Nonsteroidal antiinflammatory drugs, Angiotensin converting enzyme, Keratinocytes, T lymphocytes, Polymorphonuclear leukocytes, Makrophages, Endothelial cells, Ca binding protein psoriasin, Anthracenones, Epidermal growth factor, Endothelial leukocyte adhesion molecule 1, Interleukin, Lactate dehydrogenase, 5 Lipoxygenase, Platelet activating factor, Vascular cell adhesion molecule 1