Nucleotide analogs related to acyclovir and ganciclovir are effective against murine cytomegalovirus infections in BALB/c and severe combined immunodeficient mice.

Abstract

Acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; SR3722] and the S enantiomer (SR3772), R enantiomer (SR3773), and R,S enantiomeric mixture (SR3745A) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine) were evaluated for their antiviral activities against murine cytomegalovirus. In severe combined immunodeficient mice infected with murine cytomegalovirus, SR3773 and SR3745A (12.5, 25, and 50 mg/kg of body weight per day) were superior to ganciclovir in extending the mean time to death, whereas SR3722 and SR3772 was less potent than ganciclovir. In normal BALB/c mice, SR3773 and ganciclovir were approximately equally active in preventing death. SR3773 caused renal tubular damage when administered at 50 mg/kg/day for 15 days. These results suggest that SR3773 may have potential for use in the treatment of human cytomegalovirus infections, but it may also exhibit renal toxicity.

• Authors: D F Smee, S T Sugiyama, E J Reist
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 38 Issue 9 Pg. 2165-8 (Sep 1994) ISSN: 0066-4804 [Print] United States
• PMID: 7811037 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Nucleotides
• Ganciclovir
• Acyclovir

Topics

• Acyclovir (analogs & derivatives, pharmacology)
• Animals
• Antiviral Agents (pharmacology)
• Disease Models, Animal
• Female
• Ganciclovir (analogs & derivatives, pharmacology)
• Herpesviridae Infections (drug therapy, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Microbial Sensitivity Tests
• Muromegalovirus
• Nucleotides (pharmacology)
• Stereoisomerism