Bosca F, Encinas S, Heelis P F, Miranda M A
Departatmento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Spain.
Chem Res Toxicol. 1997 Jul;10(7):820-7. doi: 10.1021/tx9700376.
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.
卡洛芬（1a）是一种具有光敏性的非甾体抗炎药。它从三重激发态发生光脱卤反应。生成的芳基自由基（II）能够从模型脂质中提取氢原子，通过I型机制介导脂质过氧化。这种芳基自由基中间体似乎是卡洛芬所观察到的光生物学效应的原因。通过激光闪光光解直接检测该物种以及用环己二烯和萘进行猝灭实验，证实了三重态的积极参与。卡洛芬还能光敏化单线态氧的产生，量子产率为0.32。一个次要的反应途径是光脱羧反应，它从激发单重态发生，生成一种乙酰衍生物（1b）。对于脱卤光产物（2a），光脱羧生成乙基（2d）和乙酰（2b）衍生物，同时也能产生单线态氧（量子产率 = 0.18）。然而，在亚油酸光过氧化和光溶血试验中，2a的生物活性明显低于1a，这进一步证明了光脱卤在卡洛芬不良光生物学效应中起重要作用。
