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