Searching phase II enzymes inducers, from Michael acceptor-[1,2]dithiolethione hybrids, as cancer chemopreventive agents

Future Med Chem. 2015;7(7):857-71. doi: 10.4155/fmc.15.32.

Abstract

Background: Cancer chemoprevention involves the carcinogenic process prevention, delay or reverse by the administration of chemopreventive agents, which are able to suppress or block the carcinogen metabolic activation/formation. The increased activity of phase II detoxification enzymes such as quinone-reductase (QR) and glutation-S-transferase (GST) correlates with the protection against chemically-induced carcinogenesis. It has been shown that synthetic chalcones and 3H-[1,2]-dithiole-3-thiones promote expression of genes involved in chemoprevention.

Materials & methods: Herein, the induction of phase II enzymes by designed Michael acceptor-dithiolethione hybrids was studied.

Results & discussion: Hybrids 5 and 7 displayed the induction of quinone-reductase and glutation-S-transferase in vitro in the same order on the wild-type mouse-hepatoma Hepa 1c1c7 and on the aryl-hydrocarbon-nuclear-translocator (Arnt)-defective mutant BPrc1 cells indicating that 7 displays the best chemopreventive potential.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / chemical synthesis
  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Glutathione Transferase / metabolism*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Quinone Reductases / metabolism*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • 5-(4-(3-phenyl-2-propenoyloxy)phenyl)-3H-(1,2)dithiole-3-thione
  • Anticarcinogenic Agents
  • Cinnamates
  • Heterocyclic Compounds, 1-Ring
  • Quinone Reductases
  • Glutathione Transferase