Selective inhibition of Human Immunodeficiency Virus type 1 (HIV-1) by a novel family of tricyclic nucleosides

Antiviral Res. 2011 Oct;92(1):37-44. doi: 10.1016/j.antiviral.2011.05.002. Epub 2011 May 12.


Nucleoside 1, with an unusual tricyclic carbohydrate moiety, specifically inhibits HIV-1 replication while being inactive against HIV-2 or other (retro) viruses. In an attempt to increase the inhibitory efficacy against HIV-1, and to further explore the structural features required for anti-HIV-1 activity, different types of modifications have been carried out on this prototype compound. These include substitution of the ethoxy group at the C-4″ position by alkoxy groups of different length, branching, conformational freedom or functionalization. In addition, the 4″-ethoxy group has been removed or substituted by other functional groups. The role of the tert-butyldimethylsilyl (TBDMS) group at the 2' position has also been studied by preparing the corresponding 2'-deprotected derivative or by replacing it by other silyl (tert-hexyldimethylsilyl) or acyl (acetyl) moieties. Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl. Some of these compounds were endowed with a 6- to 7-fold higher selectivity than the prototype 1. The tricyclic nucleosides here described represent a novel type of selective anti HIV-1 inhibitors, targeted at the HIV-1-encoded reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Nucleosides / chemistry
  • Nucleosides / pharmacology*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship


  • Anti-HIV Agents
  • Nucleosides
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase