Comparative anti-herpesvirus activities of 9-(1,3-dihydroxy-2-propoxymethyl)guanine, acyclovir, and two 2'-fluoropyrimidine nucleosides.
9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG), was evaluated in cell culture and in animals for its inhibitory effect on herpes simplex viruses. Compounds run for comparison included acyclovir, 2'-fluoro-2'-deoxy-5-iodo-arabinofuranosylcytosine (FIAC), and 2'-fluoro-2'-deoxy-5-methyl-arabinofuranosyluracil (FMAU). In plaque reduction assays DHPG, acyclovir, FIAC, and FMAU were inhibitory to six herpes types 1 and 2 virus strains at concentrations of 0.2-2.4 microM. These concentrations were much lower than those required to inhibit Vero cell proliferation. In guinea pig vaginal infections, DHPG provided significantly greater inhibition of herpetic lesions than did acyclovir. In a herpes type 2 infection model in mice, DHPG, and FMAU were active at 5 mg/kg, whereas acyclovir and FIAC showed no statistically significant effect at 80 mg/kg. In a herpes type 1 encephalitis model, DHPG and FMAU were active at doses less than 10 mg/kg, with FMAU being about 4 times more potent than DHPG in that model.
D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D001927:Brain Diseases / Q000188:drug therapy*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003561:Cytarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004660:Encephalitis / Q000188:drug therapy; D005260:Female; D015774:Ganciclovir; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy*; D006561:Herpes Simplex / Q000188:drug therapy*; D007668:Kidney; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D003561:Cytarabine; D001086:Arabinofuranosyluracil; C026023:fiacitabine; C034935:clevudine; D015774:Ganciclovir; D000212:Acyclovir