Structural characterization and biological effects of photocyclized products of tamoxifen irradiation.
Tamoxifen (TAM) is an antiestrogen useful in the treatment and control of breast cancer. Exposure of solutions of TAM to UV irradiation produces mixtures of fluorescent derivatives that are useful in the analytical detection and quantitative determination of TAM. The two major products of such irradiations were isolated and assigned unambiguous structures based on analysis of UV and 1H NMR spectral data. Results were in accordance with earlier studies that indicated these products to be substituted phenanthrenes produced by dehydrogenation of cyclized intermediates subsequent to partial isomerization of TAM. Each of the phenanthrenes suppressed MCF-7 human breast cancer cell growth in a dose-dependent manner, but neither compound was as potent as TAM in this regard. Also, unlike treatment with TAM, cell growth could not be restored in the presence of either of the phenanthrenes by simultaneous exposure to estradiol.
Wilson
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Department of Medicinal Chemistry, College of Pharmacy, University of Georgia, Athens 30602.
Ruenitz
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PC
D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D002855:Chromatography, Thin Layer; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010616:Phenanthrenes / Q000302:isolation & purification* / Q000494:pharmacology*; D010777:Photochemistry; D013056:Spectrophotometry, Ultraviolet; D013629:Tamoxifen / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D010616:Phenanthrenes; D013629:Tamoxifen; D004958:Estradiol