Madyastha K M, Raj C P
Department of Organic Chemistry, Indian Institute of Science, Bangalore.
Biochem Biophys Res Commun. 1990 Dec 31;173(3):1086-92. doi: 10.1016/s0006-291x(05)80897-6.
Incubation of R-(+)-pulegone(I) with PB-induced rat liver microsomes in the presence of NADPH resulted in the formation of menthofuran (II) and 2-Z-[2'-keto-4'-methylcyclohexylidene] propanol (III, 9-hydroxy pulegone) as the major and minor metabolites, respectively. When isopulegone (IV) was used as the substrate, the major metabolite formed was shown to have identical GC-MS fragmentation pattern to that of synthetic 2-[2'-keto-4'-methylcyclohexyl]prop-2-en-1-ol (V) and the minor metabolite was shown to be menthofuran (II). Transformation of menthofuran (II) by microsomes in the presence of NADPH yielded a metabolite identified as 2-Z-(2'-keto-4'-methyl cyclohexylidene) propanal (VI, pulegone-8-aldehyde). Formation of this alpha, beta -unsaturated aldehyde was further confirmed by trapping it as cinnoline derivative by adding semicarbazide to the assay medium. The toxicity mediated by pulegone is discussed in the light of these observations.
在NADPH存在的情况下，将R-(+)-长叶薄荷酮（I）与PB诱导的大鼠肝微粒体一起温育，分别生成了薄荷呋喃（II）和2-Z-[2'-酮-4'-甲基环己叉基]丙醇（III，9-羟基长叶薄荷酮）作为主要和次要代谢产物。当异长叶薄荷酮（IV）用作底物时，形成的主要代谢产物显示出与合成的2-[2'-酮-4'-甲基环己基]丙-2-烯-1-醇（V）相同的GC-MS裂解模式，次要代谢产物为薄荷呋喃（II）。在NADPH存在的情况下，微粒体对薄荷呋喃（II）的转化产生了一种代谢产物，鉴定为2-Z-(2'-酮-4'-甲基环己叉基)丙醛（VI，长叶薄荷酮-8-醛）。通过向测定介质中加入氨基脲将其捕获为噌啉衍生物，进一步证实了这种α,β-不饱和醛的形成。根据这些观察结果讨论了长叶薄荷酮介导的毒性。
