title: Synthesis and antiviral evaluation of 1-O-hexadecylpropanediol-3-P-acyclovir: efficacy against HSV-1 infection in mice.
abstract: We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavailable lipid prodrug of acyclovir and evaluated it for in vitro and in vivo activity against herpes simplex virus infections. Although 1-O-hexadecylpropanediol-3-P- acyclovir was less active in vitro than acyclovir, on a molar basis it was 2.4 times more active orally in preventing mortality from acute HSV-1 infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir was also more active than acyclovir in a thymidine kinase negative mutant strain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus infection in vitro due to it's ability to bypass thymidine kinase.
authors.affiliation: Department of Medicine University of California, San Diego, La Jolla 92093-0676, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Beadle
authors.forename: G D
authors.initials: GD
authors.lastname: Kini
authors.forename: K A
authors.initials: KA
authors.lastname: Aldern
authors.forename: M F
authors.initials: MF
authors.lastname: Gardner
authors.forename: K N
authors.initials: KN
authors.lastname: Wright
authors.forename: R J
authors.initials: RJ
authors.lastname: Rybak
authors.forename: E R
authors.initials: ER
authors.lastname: Kern
authors.forename: K Y
authors.initials: KY
authors.lastname: Hostetler
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy*; D005260:Female; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: C411256:1-O-hexadecylpropanediol-3-p-acyclovir; D000998:Antiviral Agents; D011355:Prodrugs; D013937:Thymidine Kinase; D000212:Acyclovir