[Synthesis and cytotoxic properties of anomeric 5-substituted 3'-azido-2',3'-dideoxyuridines]

Bioorg Khim. 1992 Mar;18(3):444-8.
[Article in Russian]

Abstract

Glycosylation of trimethylsilyl derivatives of 5-benzyloxymethyl- and 5-hydroxymethyluracil with 3-azido-2,3-dideoxy-5-O-benzoyl-D-ribofuranosyl chloride (prepared from ethyl 3-azido-2,3-dideoxy-5-O-benzoyl-D-ribofuranoside) and subsequent deacylation gave in both cases a mixture of anomeric 3'-azido-2',3'-dideoxy-5-benzyloxymethyl-or 5-hydroxymethyluridines. The anomers were separated by preparative TLC and their structures were studied by UV, IR and 1H-NMR spectroscopy. It is shown that 1-(3-azido-2,3-dideoxy-alpha-D-ribofuranosyl)-5-benzyloxymethyluracil has cytotoxic activity in vitro: in 10(-5)-10(-4) M concentrations it inhibits the thymidine incorporation into DNA of CaOv cells on 78.6-95.2%.

Publication types

  • English Abstract

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects*
  • Chromatography, Thin Layer
  • DNA / metabolism
  • Glycosylation
  • Magnetic Resonance Spectroscopy
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Thymidine / metabolism
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis
  • Zidovudine / pharmacology

Substances

  • Antiviral Agents
  • Zidovudine
  • DNA
  • 3'-azido-2',3'-dideoxyuridine
  • Thymidine