Metabolic rate modification of nitrotriazole radiosensitizers by sulfur substitution of side chain

Int J Radiat Oncol Biol Phys. 1992;22(3):597-600. doi: 10.1016/0360-3016(92)90885-l.

Abstract

The pharmacokinetic properties and radiosensitizing activities in vitro and in vivo of a series of 3-nitro-1,2,4-triazole (NTA) derivatives with a -CH2(C = Y)NH(CH2)nZCH3 (Y, Z = O or S; n = 2 or 3) group in the side chain at N-1 position of NTA were investigated with respect, particularly, to the effects of sulfur substitution in the side chain of NTA. The sulfur substitution for an oxygen atom in the side chain NTA radiosensitizers increased the rho value, but gave rise to little effect on the one-electron reduction potential. The derivatives bearing a thioether group (-CH2SCH3) in the side chain were slightly less effective both in vitro on hypoxic EMT6/KU cells and in vivo on SCCVII tumors than their oxygen analogs (-CH2OCH3). The thioether compounds tended to metabolize rapidly. The thioamide compound showed high sensitizing activity in vitro, but metabolized very slow.

MeSH terms

  • Animals
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Cell Hypoxia / radiation effects
  • Combined Modality Therapy
  • Female
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / radiotherapy
  • Radiation-Sensitizing Agents / pharmacokinetics*
  • Radiation-Sensitizing Agents / pharmacology
  • Radiation-Sensitizing Agents / therapeutic use
  • Triazoles / pharmacokinetics*
  • Triazoles / pharmacology
  • Triazoles / therapeutic use
  • Tumor Cells, Cultured

Substances

  • Radiation-Sensitizing Agents
  • Triazoles