Inactivation of S-adenosyl-L-homocysteine hydrolase with novel 5'-thioadenosine derivatives. Antiviral effects

Bioorg Med Chem Lett. 2003 May 19;13(10):1649-52. doi: 10.1016/s0960-894x(03)00279-8.

Abstract

Synthesis of 5'-S-vinyl-5'-thioadenosine 5, 5'-S-ethynyl-5'-thioadenosine 7 and 5'-S-cyano-5'-thioadenosine 9 is described. Incubation of AdoHcy hydrolase with 5, 7 and 9 resulted in time- and concentration-dependent inactivation of the enzyme and partial depletion of its NAD(+) content. From these results and characterisation of metabolites released during the inactivation process, hypothetical mechanisms are suggested. The antiviral activity of 5, 7 and 9 was examined. Significant activities were noted with 5 against Vaccinia, Junin and Taccaribe viruses.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry*
  • Adenosine / pharmacology
  • Adenosine / toxicity
  • Adenosylhomocysteinase / antagonists & inhibitors*
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / toxicity
  • Cells, Cultured
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / toxicity
  • Humans
  • Junin virus / drug effects
  • Kinetics
  • Microbial Sensitivity Tests
  • Models, Molecular
  • NAD / chemistry
  • Thionucleosides / chemistry*
  • Thionucleosides / pharmacology
  • Thionucleosides / toxicity
  • Vaccinia virus / drug effects
  • Viruses / drug effects

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Thionucleosides
  • NAD
  • 5'-thioadenosine
  • Adenosylhomocysteinase
  • Adenosine