Correlation between the antiviral activity of acyclic and carbocyclic adenosine analogues in murine L929 cells and their inhibitory effect on L929 cell S-adenosylhomocysteine hydrolase

Abstract

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 < ( RS)-3-adenin-9-yl-2-hydroxypropanoic acid (isobutyl ester) < 3-deazaneplanocin A ~ carbocyclic 3-deazaadenosine < adenosine dialdehyde < neplanocin A. These findings point to AdoHcy hydrolase as the target for the antiviral action of these adenosine analogues.