ABSTRACT
The metabolism of 8-methoxypsoralen (8-MOP) by the yeast Saccharomyces cerevisiae has been investigated in order to determine if this cell system could provide a simple model to study the metabolism of new photosensitizing drugs in vitro. 8-MOP was found to be rapidly metabolized by S. cerevisiae in non growing conditions. A metabolite was detected which exhibits a structure similar to that of a metabolite previously isolated in dog and man. Ethanol showed a strong inducing effect on 8-MOP metabolization.
Subject(s)
Ethanol/pharmacology , Methoxsalen/metabolism , Saccharomyces cerevisiae/metabolism , Biotransformation , Chromatography, Gas , Chromatography, High Pressure Liquid , Culture Media , Gas Chromatography-Mass Spectrometry , Spectrometry, Fluorescence , Staining and Labeling , Time Factors , Ultraviolet RaysABSTRACT
The physico-chemical properties and the stability of anthralin, a potent antipsoriatic agent, has been investigated in model systems by optical absorption and fluorescence spectroscopy and by gas chromatography coupled to mass spectrometry. Systematic studies were carried out on anthralin and its oxidation products (1,8-dihydroxyanthraquinone and 1,8-1',8'-tetrahydroxydianthron). Anthralin and 1,8-dihydroxyanthraquinone are shown to readily bind to human serum albumin and not to DNA. Anthralin bound to albumin readily oxidizes, yielding the 1,8-dihydroxyanthraquinone which is fairly stable. These results are correlated with those obtained with intact whole human epidermis and suction blister fluid showing that, in the former case, anthralin binds to protein as suggested by absorption and fluorescence spectroscopies. Gas chromatography-mass spectrometry analysis makes it easy to detect anthralin and 1,8-dihydroxyanthraquinone in suction blister fluid doped with anthralin but not in suction blister obtained after topical application on normal human skin.
