KIH-802: 2-nitroimidazole-1-acetohydroxamate as a hypoxic cell radiosensitizer

Int J Radiat Oncol Biol Phys. 1989 Apr;16(4):1029-32. doi: 10.1016/0360-3016(89)90909-7.

Abstract

We have identified potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802) as a hypoxic cell radiosensitizer potentially superior to Miso. The water-soluble acetohydroxamates of 2-nitroimidazole (KIH-802; free acid 801) and 4-nitroimidazole (KIH-852) were designed, synthesized, and evaluated by in vitro and in vivo screening against EMT6 cells. Enhancement ratios of KIH-802 and 801 were 1.92 and 1.68, respectively, compared with 1.58 for MISO all at 1 mM. These acetohydroxamates are also expected to be more effective in vitro than SR-2508 based on our previous experiments. In vivo ERs of KIH-802, 801, and 852 were 1.75, 1.50, and 1.35, respectively, compared with 1.57 for MISO all at the same dose of 200 mg/kg. The data clearly show that the addition of an acetohydroxamic acid moiety to the 2-nitroimidazole skeleton can enhance radiosensitizing ability.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Hydroxamic Acids* / chemical synthesis
  • Hydroxamic Acids* / pharmacokinetics
  • Hydroxamic Acids* / pharmacology
  • In Vitro Techniques
  • Mice
  • Nitroimidazoles* / chemical synthesis
  • Nitroimidazoles* / pharmacokinetics
  • Nitroimidazoles* / pharmacology
  • Oxygen / metabolism
  • Radiation-Sensitizing Agents* / chemical synthesis
  • Radiation-Sensitizing Agents* / pharmacokinetics
  • Radiation-Sensitizing Agents* / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / radiation effects

Substances

  • Hydroxamic Acids
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • 2-nitroimidazole-1-acetohydroxamic acid
  • Oxygen