Photochemistry of 2-hydroxy-4-trifluoromethylbenzoic acid, major metabolite of the photosensitizing platelet antiaggregant drug triflusal.
Triflusal is a platelet antiaggregant drug with photoallergic side effects. However, it is considered a prodrug since it is metabolized to 2-hydroxy-4-trifluoromethylbenzoic acid (HTB)--the pharmacologically active form. HTB was found to be photolabile under various conditions. Its major photodegradation pathway appears to be the nucleophilic attack at the trifluoromethyl moiety. The involvement of the triplet state in the photodegradation has been unequivocally proved by direct detection of this transient in laser flash photolysis and by quenching experiments with oxygen, cyclohexadiene and naphthalene. Finally, the photobinding of HTB to proteins such as bovine serum albumin has been demonstrated using ultraviolet-visible (UV-Vis) and fluorescence spectroscopy. Nucleophilic groups present in the protein appear to be responsible for the formation of covalent drug photoadducts, which is the first step involved in the photoallergy shown by triflusal.
Boscá
F
F
Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Avenida de los Naranjos s/n, 46022 Valencia, Spain.
Cuquerella
M C
MC
Marín
M L
ML
Miranda
M A
MA
D017454:Dermatitis, Photoallergic / Q000209:etiology; D010777:Photochemistry; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012459:Salicylates / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; D012710:Serum Albumin, Bovine; C033502:4-trifluoromethylsalicylic acid