Formation of a perbenzoic acid derivative in the photodegradation of fenofibrate: phototoxicity studies on erythrocytes.
The phototoxic antihyperlipoproteinemic drug fenofibrate (1) is photolabile under aerobic conditions. Irradiation of a methanol solution of 1 produces, under oxygen, photoproducts 2, 3, and 4. A peroxidic photoproduct 2 was isolated and identified. The biologically active antioxidants glutathione and cysteine efficiently reduce 2 to its acid. This photoproduct was also capable of efficiently oxidizing tetramethyl phenylendiamine (TMP) through an electron transfer mechanism, detecting a TMP+ species by UV-visible spectrometry. Fenofibrate was screened in vitro at different concentrations for UV-visible-induced phototoxic effects in a photohemolysis test, under oxygen as well as argon. The photohemolysis rate was low under anaerobic conditions. No hemolysis occurred without irradiation. The isolated photoproduct 2 induced hemolysis without irradiation.
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Centro de Química, Instituto Venezolano de Investigaciones Científicas I.V.I.C., Caracas.
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D002723:Chlorobenzoates / Q000138:chemical synthesis* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000528:radiation effects; D011345:Fenofibrate / Q000528:radiation effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010100:Oxygen; D010777:Photochemistry; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
D002723:Chlorobenzoates; C040768:4-chlorobenzoic acid; D010100:Oxygen; D011345:Fenofibrate