Development of novel antipsoriatic anthrones

Antipsoriatic anthrones are among the most commonly used topical agents for the treatment of psoriasis. A large body of evidence has shown that the biochemical basis for their mechanism of action at the molecular level is related to their redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical, and hydroxyl radical. These species can react with all classes of biological macromolecules and are involved in three principal cellular effects of the anthrones: interaction with DNA, inhibition of various enzyme systems associated with cell proliferation and inflammation, and redox reactions with the resulting alteration of mitochondrial functions and destruction of membrane lipids. The application of this information to the design of novel anthrones has resulted in compounds with diminished oxygen radical generating properties which may permit a separation of antipsoriatic and inflammatory effects. In particular, 10-phenylacyl-substituted anthrones which produced significantly less amounts of oxygen radicals than the antipsoriatic anthralin compared favorably in biological tests with this known drug as an alternative method for treating psoriasis.