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.