[Inhibition of HIV reproduction in cell culture by 5'-phosphonates of 3'-azido-2',3'-dideoxynucleosides]

Mol Biol (Mosk). 1989 Nov-Dec;23(6):1716-24.
[Article in Russian]

Abstract

The antiviral activity of 3'-azido-2',3'-dideoxynucleoside 5'-phosphate analogues: 5'-phosphonomethylene-3'-azido-2',3'-dideoxythymidine, 5'-methylphosphonate and 5'-phosphite of 3'-azido-2',3'-dideoxythymidine, 5'-phosphites of 3'-azido-2',3'-dideoxyadenosine and guanosine was investigated in HIV-infected cell cultures (human lymphoblastoid cells). The effectivity of inhibition of HIV-reproduction in cells by these substances was close or even higher than that for the corresponding 3'-azido-2',3'-dideoxynucleosides, whereas their toxicity was lower than that of nucleosides. These substances are supposed to be transported into the cells and to be transformed into the corresponding 5'-triphosphate analogues under the action of cell kinases. It is possible that such agents are terminator substrates of virus reverse transcriptases and thus inhibit the biosynthesis of DNA chains.

Publication types

  • English Abstract

MeSH terms

  • Antiviral Agents* / chemical synthesis
  • Azides / chemical synthesis
  • Azides / pharmacology*
  • Cells, Cultured
  • Chemical Phenomena
  • Chemistry
  • Dideoxyadenosine / analogs & derivatives
  • Dideoxyadenosine / chemical synthesis
  • Dideoxyadenosine / pharmacology
  • Dideoxynucleosides / chemical synthesis
  • Dideoxynucleosides / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Organophosphonates / chemical synthesis
  • Organophosphonates / pharmacology
  • Virus Replication / drug effects*
  • Zidovudine / analogs & derivatives
  • Zidovudine / chemical synthesis
  • Zidovudine / pharmacology

Substances

  • Antiviral Agents
  • Azides
  • Dideoxynucleosides
  • Organophosphonates
  • Zidovudine
  • Dideoxyadenosine
  • 3'-azido-2',3'-dideoxyguanosine