Treatment of psoriasis with anthrones-chemical principles, biochemical aspects, and approaches to the design of novel derivatives.
Antipsoriatic anthrones are probably the most commonly used topical agents in the treatment of psoriasis. There is growing evidence 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 are involved in a variety of oxidative effects affecting cellular targets that have been implicated both in the mode of action and the skin-irritating properties of antipsoriatic anthrones: interaction with DNA, inhibition of various enzyme systems associated with cell proliferation and inflammation, such as glucose-6-phosphate dehydrogenase and inflammation, such as glucose-6-phosphate dehydrogenase and 5-lipoxygenase, and destruction of membrane lipids. Furthermore, the application of this information to the design of novel derivatives is discussed. In particular, compounds with diminished oxygen radical-generating properties have been developed, which may permit a separation of antipsoriatic and inflammatory effects. Some of the novel anthrone analogs which produced significantly less amounts of oxygen radicals than dithranol compared favorably in biological tests with this known antipsoriatic drug as an alternative method of treating psoriasis.
Wiegrebe
W
W
Institute of Pharmacy, University of Regensburg, Germany.
Müller
K
K
D000873:Anthracenes / Q000627:therapeutic use*; D000875:Anthralin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D015227:Lipid Peroxidation; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy*; D017382:Reactive Oxygen Species; D000095322:Anthrones
D000873:Anthracenes; D000875:Anthralin; D016859:Lipoxygenase Inhibitors; D017382:Reactive Oxygen Species; C004522:anthrone; D000095322:Anthrones