Possible molecular basis for antiviral activity of certain 5-substituted deoxyuridines.
The antiviral activity of five structurally related pyrimidine nucleosides, E-5-propenyl-2'-deoxyuridine, 5-allyl-2'-deoxyuridine, E-5-(1-butenyl)-2'-deoxyuridine, 5-(2-butenyl)-2'-deoxyuridine, and 5-butyl-2'-deoxyuridine, in cell culture against herpes simplex virus type 1 was examined. Analogs in which the C-C double bond of the 5-substituent was in conjugation with the pyrimidine ring were more potent antiviral drugs than were the corresponding nonconjugated and alkyl-substituted analogs. Differences in antiviral activity similar to those observed in cell culture occurred in virus-infected mice. The molecular basis for the greater antiviral activity of the conjugated isomers was investigated. It was observed that the conjugated isomer E-5-propenyl-2'-deoxyuridine had a greater affinity for virus thymidine kinase and, as the 5'-triphosphate, for virus DNA polymerase than did the nonconjugated isomer 5-allyl-2'-deoxyuridine. The results are discussed in relation to other data in the literature.
D000818:Animals; D000998:Antiviral Agents; D002478:Cells, Cultured; D003857:Deoxyuridine / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D019384:Nucleic Acid Synthesis Inhibitors; D010766:Phosphorylation; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D013937:Thymidine Kinase; D003857:Deoxyuridine