Propargylic sulfones possessing a 2-nitroimidazole function: novel hypoxic-cell radiosensitizers with intracellular non-protein thiol depletion ability.

Abstract

Propargylic sulfones (1a-c) containing a 2-nitroimidazole structure were synthesized, and their non-protein thiol (NPSH) depletion abilities were investigated. Propargylic sulfones 1a,c containing an electron withdrawing p-nitrophenyl group showed high reactivity toward capturing glutathione (GSH), a typical intracellular NPSH, in phosphate buffer. Among the three propargylic sulfones 1a-c, carboxylic acid derivative 1c showed the most potent radiosensitizing activity toward hypoxic EMT6/KU tumor cells. In view of these results and the partition coefficients between 1-octanol and water, we concluded that appropriate NPSH-depletion ability and lipophilicity are both important in achieving potent hypoxic-cell radiosensitization by propargylic sulfones possessing a 2-nitroimidazole function in biological systems.

• Authors: Kazuhito Tanabe, Ryusuke Kojima, Hiroshi Hatta, Sei-ichi Nishimoto
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 14 Issue 10 Pg. 2633-5 (May 17 2004) ISSN: 0960-894X [Print] England
• PMID: 15109667 (Publication Type: Journal Article)

Chemical References

• Alkynes
• Nitroimidazoles
• Radiation-Sensitizing Agents
• Sulfhydryl Compounds
• propargylic sulfone
• Isatin
• Glutathione

Topics

• Alkynes (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects, radiation effects)
• Glutathione (metabolism)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Hypoxia (metabolism)
• Isatin (analogs & derivatives, chemical synthesis, pharmacology)
• Kinetics
• Nitroimidazoles (chemistry, pharmacology)
• Radiation-Sensitizing Agents (chemical synthesis, pharmacology)
• Structure-Activity Relationship
• Sulfhydryl Compounds (metabolism)