Photophysical and photochemical characterization of a photosensitizing drug: a combined steady state photolysis and laser flash photolysis study on carprofen.
Carprofen (1a) is a photosensitizing nonsteroidal anti-inflammatory drug. It undergoes photodehalogenation from its triplet excited state. The resulting aryl radical (II) is able to abstract hydrogen atoms from model lipids, mediating their peroxidation by a type I mechanism. This aryl radical intermediate appears to be responsible for the observed photobiological effects of carprofen. The active involvement of the triplet state has been confirmed by direct detection of this species in laser flash photolysis and by quenching experiments with cyclohexadiene and naphthalene. Carprofen also photosensitizes singlet oxygen production with a quantum yield of 0.32. A minor reaction pathway is photodecarboxylation, which occurs from the excited singlet state and leads to an acetyl derivative (1b). In the case of the dehalogenated photoproduct (2a), photodecarboxylation to the ethyl (2d) and acetyl (2b) derivatives, together with singlet oxygen production (quantum yield = 0.18), is also possible. However, the biological activity of 2a in the linoleic acid photoperoxidation and photohemolysis tests is markedly lower than that of 1a, which constitutes further evidence in favor of the important role of photodehalogenation in the adverse photobiological effects of carprofen.
Bosca
F
F
Departatmento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Spain.
Encinas
S
S
Heelis
P F
PF
Miranda
M A
MA
D002227:Carbazoles / Q000737:chemistry*; D004735:Energy Transfer; D004912:Erythrocytes / Q000528:radiation effects; D005453:Fluorescence; D006461:Hemolysis; D006801:Humans; D007834:Lasers; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation; D008163:Luminescent Measurements; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D002227:Carbazoles; D017319:Photosensitizing Agents; D019787:Linoleic Acid; C007005:carprofen