Correlation between the antiviral activity of acyclic and carbocyclic adenosine analogues in murine L929 cells and their inhibitory effect on L929 cells S-adenosylhomocysteine hydrolase.
For a series of acyclic and carbocyclic adenosine analogues, a close correlation was found between their inhibitory effect on murine L929 cell S-adenosylhomocysteine (AdoHcy) hydrolase and their inhibitory effects on the replication of vaccinia virus and vesicular stomatitis virus (r: 0.993 and 0.988, respectively). In terms of their increasing inhibitory action against both virus replication and AdoHcy hydrolase activity the compounds ranked as follows: (S)-9-(2,3-dihydroxypropyl)adenine less than (RS)-3-adenin-9-yl-2-hydroxypropanoic acid (isobutyl ester) less than 3-deazaneplanocin A approximately carbocyclic 3-deazaadenosine less than adenosine dialdehyde less than neplanocin A. These findings point to AdoHcy hydrolase as the target for the antiviral action of these adenosine analogues.
Cools
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M
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
de Clercq
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E
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D000998:Antiviral Agents; D002460:Cell Line / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D051379:Mice; D014616:Vaccinia virus / Q000187:drug effects* / Q000201:enzymology; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000201:enzymology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C030034:aristeromycin; C016391:9-(2,3-dihydroxypropyl)adenine; C031096:neplanocin A; C048336:3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000225:Adenine; D000241:Adenosine