Inactivation of S-adenosyl-L-homocysteine hydrolase with novel 5'-thioadenosine derivatives. Antiviral effects.
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.
Guillerm
Georges
G
Laboratoire de Chimie Bioorganique, UMR 6519, UFR Sciences, B.P. 1039, 51687 Reims cedex 2, France. georges.guillerm@univ-reims.fr
Guillerm
Danielle
D
Vandenplas-Vitkowski
Corinne
C
Glapski
Cédric
C
De Clercq
Erick
E
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D018051:Junin virus / Q000187:drug effects; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry; D013872:Thionucleosides / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D014616:Vaccinia virus / Q000187:drug effects; D014780:Viruses / Q000187:drug effects
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D013872:Thionucleosides; D009243:NAD; C063476:5'-thioadenosine; D043383:Adenosylhomocysteinase; D000241:Adenosine