5'-Hydrogenphosphonates of anti-HIV nucleoside analogues revisited: controversial mode of action

Antiviral Res. 1993 Oct;22(2-3):143-53. doi: 10.1016/0166-3542(93)90092-w.

Abstract

The monomeric and symmetrical dimeric 5'-hydrogenphosphonate derivatives of AZT were prepared and evaluated for their inhibitory properties against HIV-1 in several cell lines. The synthesis of the compounds was achieved by reaction of AZT with in situ prepared phosphorus tris(imidazolide) or with phosphonic acid in the presence of pivaloyl chloride. The two title compounds showed in vitro anti-HIV activity similar to (but not better than) that of AZT in three cell lines which were not deficient in thymidine kinase. On the other hand they were inactive in CEM-TK- cells. Pharmacokinetic studies in several media corroborate the assumption that these compounds must not be considered as 'true antiviral agents', but that they act by releasing their nucleoside entity.

Publication types

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

MeSH terms

  • Cell Line
  • Dideoxynucleotides
  • Drug Stability
  • HIV-1 / drug effects*
  • Humans
  • Prodrugs / metabolism
  • T-Lymphocytes / cytology
  • Thymine Nucleotides / pharmacology
  • Virus Replication / drug effects
  • Zidovudine / analogs & derivatives*
  • Zidovudine / pharmacology

Substances

  • Dideoxynucleotides
  • Prodrugs
  • Thymine Nucleotides
  • 3'-azido-3'-deoxythymidine 5'phosphate
  • Zidovudine