Photochemistry and phototoxicity studies of flutamide, a phototoxic anti-cancer drug.
The phototoxic anti-cancer drug flutamide is photolabile under UV-B light in either aerobic or anaerobic conditions. Irradiation of a methanol solution of this drug produces several photoproducts, one by photoreduction of the nitro group, one by rupture of the aromatic-NO2 bond of the parent compound, two as a result of the rupture of the CO-NH bond and one derived from the photoreduction product by scission of the aromatic-NH2 bond. Flutamide shows a photohemolytic effect on human erythrocytes and photoinduces lipid peroxidation. Studies on peripheral blood polymorphonuclear cells (neutrophils) demonstrated the phototoxicity of flutamide as well as inhibition of the cytotoxicity respiratory burst by the photoproduct derived from its photoreduction. The results suggest that the inhibition of the respiratory burst observed in phorbol myristate acetate (PMA)-activated cells is mediated by photosensitization and concomitant singlet oxygen production and/or formation of toxic photoproducts.
Laboratorio de Fotoqulimica, Centro de Química, Instituto Venezolano de Investigaciones Científicas IVIC., Caracas, Venezuela.
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Vargas
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Rivas
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Méndez
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Fraile
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Velásquez
D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000528:radiation effects* / Q000633:toxicity*; D005485:Flutamide / Q000737:chemistry / Q000528:radiation effects* / Q000633:toxicity*; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000528:radiation effects; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000528:radiation effects; D018462:Photobiology; D010777:Photochemistry; D010782:Photolysis; D012709:Serum Albumin / Q000528:radiation effects; D014466:Ultraviolet Rays
D018931:Antineoplastic Agents, Hormonal; D012709:Serum Albumin; D005485:Flutamide