RESUMO
First of all some general concepts are given on phototoxic activity of pharmaceutical products which full fill the structural characteristics required to decompose by light and to cause biological damage, either themselves, their photoproducts or the products of their metabolism. These considerations are important due to the fact that this field of research is fairly new. Next, a review is given on recent research carried out in this laboratory on the photochemistry and phototoxicity of fibric acid and their derivatives and finally a review is made as well on the photochemistry and phototoxicity of antibacterial quinolones. Mechanisms are postulated for the photochemical decomposition of the substances investigated and possible mechanism for the in vitro activity at cellular level are also presented.
Assuntos
Dermatite Fototóxica/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , 4-Quinolonas , Anti-Infecciosos/toxicidade , Butiratos/toxicidade , Fenofibrato/toxicidade , Genfibrozila/toxicidade , Hipolipemiantes/toxicidade , Fotoquímica , FotóliseRESUMO
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.
Assuntos
Clorpropamida/química , Hipoglicemiantes/química , Antioxidantes/farmacologia , Clorpropamida/efeitos da radiação , Clorpropamida/toxicidade , Eritrócitos/efeitos da radiação , Hemólise/efeitos dos fármacos , Hemólise/efeitos da radiação , Humanos , Hipoglicemiantes/efeitos da radiação , Hipoglicemiantes/toxicidade , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Fotoquímica , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Benzydamine hydrochloride (Tantum, 1) is a photoallergic and phototoxic anti-inflammatory and analgesic agent. This drug is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of benzydamine under oxygen or argon at 300 nm affords 5-hydroxybenzydamine (2) and 2-beta-dimethylaminopropyl-1-benzylindalolin-3-one (3) as the main isolated and spectroscopically identified photoproducts. A radical intermediate was evidenced by thiobarbituric acid that was used as a radical sonde, as well as by the dimerization of cysteine. Erythrocyte lysis photosensitized by 1, 2, and 3 was investigated.