The phosphate-group of DNA as a potential target for RSU-1069, a nitroimidazole-aziridine radiosensitizer

Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1203-6. doi: 10.1016/0360-3016(86)90258-0.

Abstract

Strand breakage of plasmid DNA by parent and radiation-reduced RSU-1069 (2.0-8.0 mmol dm-3) has been measured in air over 4 hr at 310K. Reduced RSU-1069 was shown to be approximately 4 times as efficient as the parent compound at causing strand breakage. The aziridine moiety of both parent and reduced RSU-1069 is required for strand break production and, furthermore, is capable of alkylating inorganic phosphate (k = 1.0 X 10(-3) dm3 mol-1 s-1) and a series of nucleotides (k = 0.8 - 2.1 X 10(-3) dm3 mol-1 s-1) at pH 7.0. From the determined rate constants and the nature of the adducts observed, it was shown that phosphate is a target on nucleotides, although additional sites probably exist particularly, on dGMP and dAMP. The mechanism of action of RSU-1069 is discussed in terms of its ability to act as a cytotoxic agent, radiosensitizer and bioreductive drug.

MeSH terms

  • DNA, Bacterial*
  • Misonidazole / analogs & derivatives*
  • Misonidazole / pharmacology
  • Plasmids*
  • Radiation-Sensitizing Agents / pharmacology*

Substances

  • DNA, Bacterial
  • Radiation-Sensitizing Agents
  • 1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol
  • Misonidazole