title: Photodegradation and in vitro phototoxicity of the antidiabetic drug chlorpropamide.
abstract: Methanolic solutions of the phototoxic antidiabetic drug chlorpropamide (CAS 94-20-2, 1) are photolabile towards UVB light under aerobic conditions. Irradiation of 1 produces the formation of the stable compounds p-chlorobenzenesulfonamide (2), N-(p-chlorophenylsulfonyl)formamide (3) and the dimer 4. A radical intermediate was evidenced by thiobarbituric acid that was used as a radical sonde, as well as by the dimerization of cysteine. The compound 1 showed moderate lytic activity upon the photohemolysis in vitro test on human erythrocytes which was increased with the addition of traces of its aggregate excipient. Inhibition of this process on addition of reduced glutathione (GSH), superoxide dismutase (SOD) or ascorbic acid suggests the involvement of radicals and superoxide ion in the photohemolysis process. The absence of inhibition with 1,4-diazabicyclo[2.2.2]octane (DABCO) and sodium azide (NaN3), and the lack of formation of singlet oxygen during the photolysis (confirmed with 2,5-dimethylfuran) rule out the possibility of participation of 1O2 in this process. Glutathione depletion was also observed. No photohemolysis was detected in the presence of the isolated photoproduct.
authors.affiliation: Laboratorio de Fotoquímica Orgánica, Centro de Química, Instituto Venezolano de Investigaciones Cientificas I.V.I.C., Caracas, Venezuela.
authors.forename: F
authors.initials: F
authors.lastname: Vargas
authors.forename: V
authors.initials: V
authors.lastname: Matskevitch
authors.forename: Z
authors.initials: Z
authors.lastname: Sarabia
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002747:Chlorpropamide / Q000737:chemistry* / Q000528:radiation effects / Q000633:toxicity; D004912:Erythrocytes / Q000528:radiation effects; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000528:radiation effects / Q000633:toxicity; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010777:Photochemistry; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents; D002747:Chlorpropamide