Antiviral activity of 9-[[(ethoxyhydroxyphosphinyl)-methoxy]methoxy]guanine against cytomegalovirus and herpes simplex virus

Hun Taek Kim, Dae Kee Kim, Young Woo Kim, Key H. Kim, Yoshihiro Sugiyama, Mikio Kikuchi

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

An isosteric analog of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG), 9-[[(ethoxyhydroxyphosphinyl)methoxy]methoxy]guanine (SKI 1008), was evaluated for its in vitro antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), murine cytomegalovirus (MCMV), and human cytomegalovirus (HCMV), and its in vivo antiviral efficacy against MCMV in mice. The in vitro anti-HSV activity of SKI 1008 was much lower than that of acyclovir, even though SKI 1008 showed similar antiviral activity against thymidine kinase positive (TK+) and thymidine kinase negative (TK-) strains. Like ganciclovir and PMEG, SKI 1008 selectively inhibited plaque formation of MCMV; the 50% effective concentration (EC50) and the 50% cytotoxic concentration (CC50) of SKI 1008, ganciclovir, and PMEG being 0.51 and 600, 1.65 and 461, and 0.06 and 12.1 μg/ml, respectively. The in vitro EC50 value of SKI 1008 against HCMV was comparable to that of ganciclovir (0.24 vs 0.16 μg/ml) and was 12-fold higher than that of PMEG in a plaque reduction assay, but the therapeutic indices (the ratios of CC50 to EC50) of SKI 1008 and ganciclovir were higher than that of PMEG. The in vivo antiviral efficacy of SKI 1008 in MCMV-infected normal BALB/c and severe combined immunodeficiency (SCID) mice was lower than that of ganciclovir in terms of mortality and mean survival time.

Original languageEnglish
Pages (from-to)243-251
Number of pages9
JournalAntiviral Research
Volume28
Issue number3
DOIs
StatePublished - Nov 1995

Keywords

  • 9-[[(Ethoxyhydroxyphosphinyl)-methoxy]methoxy]guanine (SKI 1008)
  • Antiviral activity
  • Cytomegalovirus
  • Herpes simplex virus

Fingerprint

Dive into the research topics of 'Antiviral activity of 9-[[(ethoxyhydroxyphosphinyl)-methoxy]methoxy]guanine against cytomegalovirus and herpes simplex virus'. Together they form a unique fingerprint.

Cite this