Synthesis and Antiviral Evaluation of 1-O-Hexadecylpropanediol-3-P-acyclovir: Efficacy Against HSV-1 Infection in Mice

作者：James R. Beadle, Ganesh D. Kini, Kathy A. Aldern, Michael F. Gardner, Kristine N. Wright, Rachel J. Rybak, Earl R. Kern, Karl Y. Hostetler · 发表于：Nucleosides Nucleotides & Nucleic Acids · 年份：2000 · DOI：10.1080/15257770008033022 · 被引用次数：17 · 研究领域：Herpesvirus Infections and Treatments、Cytomegalovirus and herpesvirus research、Natural product bioactivities and synthesis

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.