Mizutani T, Yoshida K, Kawazoe S
Department of Food Science and Nutrition, Kyoto Prefectural University, Japan.
Drug Metab Dispos. 1994 Sep-Oct;22(5):750-5.
The metabolism of three nephro- or hepatotoxic thiazoles--2-(thiazol-4-yl)benzimidazole (thiabendazole) (1a), 4-tert-butyl-2-methyl-thiazole (1b), and 2-(p-methoxyphenyl)-4-methylthiazole (1c)--was examined in mice with special regard to the formation of ring cleavage products. By GC/MS analyses of derivatized metabolites and comparison with authentic samples, thioformamide and benzimidazol-2-ylglyoxal as the accompanying fragment were identified as urinary metabolites in mice dosed with 1a. Similarly, 1b produced thioacetamide and tert-butylglyoxal, and 1c produced p-methoxy-thiobenzamide (and its S-oxide) and methylglyoxal. These results could be explained by the postulated metabolic pathways where thiazoles would undergo microsomal epoxidation of the C = C double bond and, after being hydrolyzed, the resulting epoxide would then be decomposed to form the corresponding thioamides and alpha-dicarbonyl fragments.
研究了三种具有肾毒性或肝毒性的噻唑类化合物——2-(噻唑-4-基)苯并咪唑（噻苯达唑）(1a)、4-叔丁基-2-甲基噻唑(1b)和2-(对甲氧基苯基)-4-甲基噻唑(1c)——在小鼠体内的代谢情况，特别关注其开环产物的形成。通过对衍生化代谢产物进行气相色谱/质谱分析并与标准样品进行比较，确定在给小鼠服用1a后，硫代甲酰胺和苯并咪唑-2-基乙二醛作为伴随片段是尿液代谢产物。同样，1b产生硫代乙酰胺和叔丁基乙二醛，1c产生对甲氧基硫代苯甲酰胺（及其S-氧化物）和甲基乙二醛。这些结果可以用假定的代谢途径来解释，即噻唑类化合物会经历C = C双键的微粒体环氧化反应，水解后，生成的环氧化物会分解形成相应的硫代酰胺和α-二羰基片段。
