The antipsoriatic compound anthralin influences bioenergetic parameters and redox properties of energy transducing membranes.

Bioenergetic parameters and redox properties of energy transducing membranes in rat liver mitochondria and cyanobacteria were investigated in the presence of the antipsoriatic compound anthralin (1,8-dihydroxy-9-anthrone). Transmembrane pH and electrical gradients were determined using electron paramagnetic resonance spectroscopy. In mitochondria, ubiquinones 9,10 and other redox components of the electron transport chain are reduced by anthralin; the proton motive force is increased. In the absence of ADP, anthralin slightly stimulates mitochondrial cyanide-insensitive oxygen consumption. It is suggested that increased cyanide-insensitive respiration is due to enhanced autoxidation of mitochondrial components and/or catalyzed oxidation of anthralin. In the presence of ADP mitochondrial respiration is decreased, and ATP synthesis is inhibited. Uncoupler-induced mitochondrial respiration is also decreased by anthralin, indicating inhibition of the electron transport chain. In the cyanobacterium Synechococcus PCC 6311 anthralin increases the pH gradient and decreases ATP levels. Thus, anthralin acts as an electron donor to membrane associated redox components and inhibits ATP synthesis in two different biologic systems. In human keratinocytes oxygen metabolism is influenced by anthralin in a similar pattern as in isolated mitochondria, and ATP content is decreased. Because anthralin reacts with redox components in different biologic membranes, alterations of subcellular/cellular redox status and energy metabolism might contribute significantly to its antiproliferative activity.