Vargas F, Matskevitch V, Sarabia Z
Laboratorio de Fotoquímica Orgánica, Centro de Química, Instituto Venezolano de Investigaciones Cientificas I.V.I.C., Caracas, Venezuela.
Arzneimittelforschung. 1995 Oct;45(10):1079-81.
Methanolic solutions of the phototoxic antidiabetic drug chlorpropamide (CAS 94-20-2, 1) are photolabile towards UVB light under aerobic conditions. Irradiation of 1 produces the formation of the stable compounds p-chlorobenzenesulfonamide (2), N-(p-chlorophenylsulfonyl)formamide (3) and the dimer 4. A radical intermediate was evidenced by thiobarbituric acid that was used as a radical sonde, as well as by the dimerization of cysteine. The compound 1 showed moderate lytic activity upon the photohemolysis in vitro test on human erythrocytes which was increased with the addition of traces of its aggregate excipient. Inhibition of this process on addition of reduced glutathione (GSH), superoxide dismutase (SOD) or ascorbic acid suggests the involvement of radicals and superoxide ion in the photohemolysis process. The absence of inhibition with 1,4-diazabicyclo[2.2.2]octane (DABCO) and sodium azide (NaN3), and the lack of formation of singlet oxygen during the photolysis (confirmed with 2,5-dimethylfuran) rule out the possibility of participation of 1O2 in this process. Glutathione depletion was also observed. No photohemolysis was detected in the presence of the isolated photoproduct.
光毒性抗糖尿病药物氯磺丙脲（CAS 94 - 20 - 2，1）的甲醇溶液在有氧条件下对UVB光不稳定。照射1会生成稳定化合物对氯苯磺酰胺（2）、N -（对氯苯基磺酰基）甲酰胺（3）和二聚体4。用硫代巴比妥酸作为自由基探测器以及通过半胱氨酸的二聚化证明了存在自由基中间体。化合物1在对人红细胞的体外光溶血试验中表现出中等程度的溶血活性，加入微量其聚集辅料后该活性增强。加入还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）或抗坏血酸对该过程的抑制表明自由基和超氧离子参与了光溶血过程。1,4 - 二氮杂双环[2.2.2]辛烷（DABCO）和叠氮化钠（NaN3）没有抑制作用，并且光解过程中没有单线态氧生成（用2,5 - 二甲基呋喃证实），排除了单线态氧参与此过程的可能性。还观察到谷胱甘肽耗竭。在分离的光产物存在下未检测到光溶血。
