Alvaro R F, Wislocki P G, Miwa G T, Lu A Y
Department of Animal and Exploratory Drug Metabolism, Merck Sharp and Dohme Research Laboratories, Rahway, NJ 07065.
Chem Biol Interact. 1992 Mar;82(1):21-30. doi: 10.1016/0009-2797(92)90011-9.
Ronidazole protein-bound adducts were generated by the in vitro anaerobic incubation of [2-methylene-14C]ronidazole with microsomes from the livers of male rats. Acid hydrolysis of the protein adducts yielded an imidazole ring fragment bearing the radiolabel and an amino acid residue derived from the proteins. This fragment has been identified as carboxymethylcysteine by co-chromatography of the amino acid and its dansyl derivative with known standards under a variety of conditions. The carboxymethylcysteine was estimated to represent at least 15% of the radioactivity derived from the protein-bound adducts and provides unequivocal evidence that nucleophilic attack by protein cysteine thiols occurred at the 2-methylene position of ronidazole.
罗硝唑蛋白结合加合物是通过将[2-亚甲基-¹⁴C]罗硝唑与雄性大鼠肝脏微粒体进行体外厌氧孵育而产生的。蛋白加合物的酸水解产生了带有放射性标记的咪唑环片段和源自蛋白质的氨基酸残基。在多种条件下，通过将该氨基酸及其丹磺酰衍生物与已知标准品进行共色谱分析，已将该片段鉴定为羧甲基半胱氨酸。据估计，羧甲基半胱氨酸至少占源自蛋白结合加合物的放射性的15%，并提供了明确的证据，表明蛋白质半胱氨酸硫醇在罗硝唑的2-亚甲基位置发生了亲核攻击。
