Synthesis and evaluation of some novel phosphate and phosphinate derivatives of araA. Studies on the mechanism of action of phosphate triesters

Nucleic Acids Res. 1989 Dec 25;17(24):10171-7. doi: 10.1093/nar/17.24.10171.

Abstract

A number of novel phosphinate and phosphate triester derivatives of the anti-viral nucleoside analogue araA have been prepared. Spectroscopic and analytical data have been collected on both the reagents and the nucleotides. An in vitro assay indicated inhibition of DNA synthesis by mammalian cells, by each of the nucleotide derivatives, in the range 3-30 microM. Inhibition was reduced, but not abolished, for the phosphinates relative to the phosphates. These results are consistent with a mode of action involving release of the free nucleoside araA and the nucleotide araAMP.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • DNA / antagonists & inhibitors
  • DNA / biosynthesis
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Phosphates*
  • Phosphinic Acids*
  • Structure-Activity Relationship
  • Vidarabine / analogs & derivatives*
  • Vidarabine / chemical synthesis
  • Vidarabine / pharmacology

Substances

  • Phosphates
  • Phosphinic Acids
  • DNA
  • Vidarabine