Antiherpes activity of [E]-5-(1-propenyl)-2'-deoxyuridine and 5-(1-propenyl)-1-beta-D-arabinofuranosyluracil.

5-(1-Propenyl)-1-beta-D-arabinofuranosyluracil has been synthesized, and this compound and [E]-5-(-propenyl)-2'-deoxyuridine have been tested for inhibition of herpes virus multiplication. Only [E]-5-(1-propenyl)-2'-deoxyuridine was found to be an active inhibitor reducing by 50% the plaque formation of herpes simplex virus type 1 (HSV-1) at about 1 muM. A comparison to the bromovinyl derivatives showed the following order of descending activity; [E]-5-(2-bromovinyl)-2'-deoxyuridine greater than 5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil greater than or equal to [E]-5-(1-propenyl)-2'-deoxyuridine greater than 5-(1-propenyl)-1-beta-arabinofuranosyluracil. HSV-1 mutants lacking thymidine kinase or resistant against acycloguanosine were resistant against [E]-5-(1-propenyl)-2'-deoxyuridine. All compounds seemed to be phosphorylated by HSV-1 thymidine kinase in a cell-free assay. The compounds were phosphorylated to a lower extent by cellular or HSV-2 thymidine kinase, and the HSV-2 strains tested were inhibited by less than 50% at 100 muM in plaque assays. A selective inhibition of HAV-1 DNA synthesis by [E]-5-(1-propenyl)-2'-deoxyuridine was observed in infected cells indicating an effect on viral DNA polymerase. [E]-5-(1-Propenyl)-2'-deoxyuridine had a low cellular toxicity and a therapeutic effect when applied topically to HSV-1-infected guinea pig skin.