1,2-Dithiol-3-thione analogs: effects on NAD(P)H:quinone reductase and glutathione levels in murine hepatoma cells.
1,2-Dithiol-3-thione analogs: effects on NAD(P)H:quinone reductase and glutathione levels in murine hepatoma cells.
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1,2-二硫醇-3-硫酮类似物：对小鼠肝癌细胞中 NAD(P)H:醌还原酶和谷胱甘肽水平的影响。
作者：
M. D. Long;Patrick Dolan;Annette B. Santamaria;Ernest Bueding
1，2-二硫醇-3-硫酮是一类具有化疗和化学保护性质的五元环硫化合物。母体1，2-二硫醇-3-甲硫氨酸核和一系列六种取代的类似物均诱导培养的Hepa 1c 1c 7鼠肝癌细胞中NAD（P）H：醌还原酶（EC 1.6.99.2）活性和升高的谷胱甘肽水平，从而增强解毒潜力。这些类似物包括在C-4或C-5处具有苯基、对甲氧基苯基或2-吡嗪基的单取代衍生物，以及在C-5处具有苯基或2-吡嗪基部分并且在C-4处具有另外的甲基的二取代化合物。该系统可用作研究1，2-二硫醇-3-硫酮的特异性和作用机制的体外模型，这已被证明是其他几类化学保护剂。1，2-二巯基-3-硫酮还升高了Hepa 1c 1c 7细胞突变体（BPrc 1和TAOBPrc 1）中的醌还原酶和谷胱甘肽水平，这些突变体在芳烃受体功能方面存在缺陷。我们的结论是，1，2-二巯基-3-硫酮在很大程度上与刺激亲电试剂的代谢失活有关。
The 1,2-dithiol-3-thiones are a class of five-membered cyclic sulfur compounds which have chemotherapeutic and chemoprotective properties. The parent 1,2-dithiol-3-thione nucleus and a series of six substituted analogs all induced NAD(P)H: quinone reductase (EC 1.6.99.2) activity and elevated glutathione levels in Hepa 1c1c7 murine hepatoma cells in culture thereby enhancing detoxification potential. These analogs included monosubstituted derivatives with phenyl, p-methoxyphenyl or 2-pyrazinyl groups at C-4 or C-5, and disubstituted compounds bearing phenyl or 2-pyrazinyl moieties at C-5 and an additional methyl group at C-4. This system can be used as an in vitro model for the study of the specificity and mechanism of action of the 1,2-dithiol-3-thiones as already demonstrated for several other classes of chemoprotective agents. The 1,2-dithiol-3-thiones also elevated quinone reductase and glutathione levels in the Hepa 1c1c7 cell mutants (BPrc1 and TAOBPrc1) that are defective in aryl hydrocarbon receptor functions. We conclude that the 1,2-dithiol-3-thiones are largely concerned with the stimulation of metabolic inactivation of electrophiles.