Antipsoriatic drug action of anthralin: Oxidation reactions with peroxidizing lipids

Abstract

Reactions of anthralin with peroxidizing lipid were investigated. Using ESR spectroscopy and quantitative HPLC analysis radical species and decomposition products respectively were analysed in the reaction mixture as a function of time. Directly after mixing anthralin with peroxidized lipids, the 1,8-dihydroxy-9-anthron-10-yl radicals (primary radical) and small amounts of 1,8-dihydroxy-anthraquinone (AQ) were formed. After a few days of reaction, two secondary radicals were observed in addition to the primary radical. At the same time, 1,8,1′8′-tetrahydroxy-10,10′-bis-9(10H)-anthrone (DI) and an increasing amount of AO and other nonidentified decomposition products were found. As the reaction proceeded further on the amount of AQ and the nonidentified decomposition products increased, the primary radical disappeared (within about 40 d) and the concentration of DI decreased to zero (within 1 yr). Nonidentified decomposition products are tentatively assigned to polymeric degradation product (anthralin brown) formed from DI via the observed secondary radical species. These radical reactions of anthralin with peroxidized lipids help to elucidate speculations on radical type reactions of anthralin in psoriasis indications, e.g., the role of peroxidized skin lipids as radical reaction initiators.