Encinas S, Bosca F, Miranda M A
Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Avenida de los Naranjos s/n, 46022 Valencia, Spain.
Chem Res Toxicol. 1998 Aug;11(8):946-52. doi: 10.1021/tx9800708.
Diclofenac (1) is a photosensitizing nonsteroidal antiinflammatory drug. Its photodecomposition gives rise to chlorocarbazole 2a. This product undergoes photodehalogenation to 3a in a subsequent step. When the photobiological activities of 1, 2a, and 3a are compared by means of the photohemolysis test, it is clearly observed that chlorocarbazole 2a causes cell lysis with a markedly higher efficiency than the parent drug or the secondary photoproduct 3a. Laser flash photolysis studies suggest that photodehalogenation of 2a occurs from its excited triplet state via quenching by ground-state 2a and formation of an excimer. As a consequence, an aryl radical plus an N-centered carbazolyl radical are formed. These radical intermediates appear to be responsible for the observed photobiological effects of diclofenac, via hydrogen abstraction from the target biomolecules, which initiates a type-I photodynamic effect. The efficient peroxidation of model lipids, such as linoleic acid, photosensitized by 2a are in favor of this proposal. Thus, the photosensitizing properties of diclofenac appear to be associated with the photochemical and photobiological activity of its major photoproduct.
双氯芬酸（1）是一种具有光敏性的非甾体抗炎药。其光分解会产生氯代咔唑2a。该产物在后续步骤中会发生光脱卤反应生成3a。当通过光溶血试验比较1、2a和3a的光生物学活性时，可以清楚地观察到氯代咔唑2a导致细胞裂解的效率明显高于母体药物或二级光产物3a。激光闪光光解研究表明，2a的光脱卤反应是从其激发三重态通过基态2a的猝灭和激基缔合物的形成而发生的。结果，形成了一个芳基自由基和一个以N为中心的咔唑基自由基。这些自由基中间体似乎是双氯芬酸观察到的光生物学效应的原因，它们通过从目标生物分子中夺取氢引发I型光动力效应。由2a光敏化的模型脂质（如亚油酸）的有效过氧化支持了这一观点。因此，双氯芬酸的光敏特性似乎与其主要光产物的光化学和光生物学活性有关。
