Synthesis and antiviral evaluation of 1-O-hexadecylpropanediol-3-P-acyclovir: efficacy against HSV-1 infection in mice
| Autor: | Michael F. Gardner, Karl Y. Hostetler, Kristine N. Wright, James R. Beadle, Earl R. Kern, Ganesh D. Kini, Kathy A. Aldern, Rachel J. Rybak |
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| Rok vydání: | 2000 |
| Předmět: |
viruses
Acyclovir Administration Oral Cytomegalovirus HSL and HSV Herpesvirus 1 Human medicine.disease_cause Biochemistry Antiviral Agents Thymidine Kinase Mice In vivo 1-O-hexadecylpropanediol-3-p-acyclovir Genetics medicine Animals heterocyclic compounds Prodrugs Mice Inbred BALB C Chemistry virus diseases General Medicine biochemical phenomena metabolism and nutrition Prodrug Virology In vitro Bioavailability Herpes simplex virus Thymidine kinase Mutation Molecular Medicine Female Encephalitis Herpes Simplex |
| Zdroj: | Nucleosides, nucleotidesnucleic acids. 19(1-2) |
| ISSN: | 1525-7770 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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