9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication.
A new compound, 9-(3,4-dihydroxybutyl)guanine, has been synthesized and its antiherpes activity determined. 9-(3,4-Dihydroxybutyl)guanine was selectively phosphorylated by herpes simplex virus thymidine kinase and had a high affinity for this enzyme, with an inhibition constant of 1.5 microM. In cell culture, replication of different strains of herpes simplex virus types 1 and 2 was inhibited to the extent of 50% by 4 to 18 microM (RS)-9-(3,4-dihydroxybutyl)guanine. The (R)-enantiomer of this compound was more inhibitory than the (S)-enantiomer. Herpesvirus DNA synthesis was selectively inhibited by (RS)-9-(3,4-dihydroxybutyl)guanine in infected cells, and a low cellular toxicity was observed. (RS)-9-(3,4-Dihydroxybutyl)guanine had a therapeutic effect when applied topically to guinea pigs with cutaneous herpes simplex type 1 infections and to rabbits with herpes keratitis. Oral treatment of a generalized herpes simplex type 2 infection in mice had a therapeutic effect.
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology; D000998:Antiviral Agents; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D010766:Phosphorylation; D018139:Simplexvirus / Q000187:drug effects*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004279:DNA, Viral; C037591:buciclovir; D013937:Thymidine Kinase; D000212:Acyclovir