De Long M J, Dolan P, Santamaria A B, Bueding E
Carcinogenesis. 1986 Jun;7(6):977-80. doi: 10.1093/carcin/7.6.977.
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.
1,2 - 二硫醇 - 3 - 硫酮是一类具有化学治疗和化学保护特性的五元环状硫化合物。母体1,2 - 二硫醇 - 3 - 硫酮核以及一系列六种取代类似物均能诱导培养的Hepa 1c1c7小鼠肝癌细胞中的NAD(P)H：醌还原酶（EC 1.6.99.2）活性并提高谷胱甘肽水平，从而增强解毒潜力。这些类似物包括在C - 4或C - 5位带有苯基、对甲氧基苯基或2 - 吡嗪基的单取代衍生物，以及在C - 5位带有苯基或2 - 吡嗪基部分且在C - 4位带有额外甲基的双取代化合物。该系统可作为体外模型，用于研究1,2 - 二硫醇 - 3 - 硫酮的特异性和作用机制，这已在其他几类化学保护剂中得到证实。1,2 - 二硫醇 - 3 - 硫酮还能提高芳烃受体功能有缺陷的Hepa 1c1c7细胞突变体（BPrc1和TAOBPrc1）中的醌还原酶和谷胱甘肽水平。我们得出结论，1,2 - 二硫醇 - 3 - 硫酮主要与刺激亲电试剂的代谢失活有关。
