1,2-Dithiol-3-thione analogs: effects on NAD(P)H:quinone reductase and glutathione levels in murine hepatoma cells.

Abstract

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.

• Authors: M J De Long, P Dolan, A B Santamaria, E Bueding
• Journal: Carcinogenesis (Carcinogenesis) Vol. 7 Issue 6 Pg. 977-80 (Jun 1986) ISSN: 0143-3334 [Print] England
• PMID: 3708758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Thiones
• Thiophenes
• Quinone Reductases
• Glutathione
• 1,2-dithiol-3-thione

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line
• Dose-Response Relationship, Drug
• Enzyme Induction
• Glutathione (analysis)
• Liver Neoplasms, Experimental (metabolism)
• Mice
• Mutation
• Quinone Reductases (biosynthesis)
• Structure-Activity Relationship
• Thiones (pharmacology)
• Thiophenes (pharmacology)