title: Antiherpes activity of [E]-5-(1-propenyl)-2'-deoxyuridine and 5-(1-propenyl)-1-beta-D-arabinofuranosyluracil.
abstract: 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.
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives*; D001087:Arabinonucleosides / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000096:biosynthesis; D004279:DNA, Viral / Q000096:biosynthesis; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000188:drug therapy*; D010766:Phosphorylation; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D001087:Arabinonucleosides; D004279:DNA, Viral; D001086:Arabinofuranosyluracil; C032386:5-(1-propenyl)-2'-deoxyuridine; C033957:5-(1-propenyl)-1-arabinofuranosyluracil; D004247:DNA; D013936:Thymidine; D003857:Deoxyuridine; D014529:Uridine