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6-N-substituted derivatives of adenine arabinoside as selective inhibitors of varicella-zoster virus.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 1991 Jul; Vol. 35 (7), pp. 1437-43. - Publication Year :
- 1991
-
Abstract
- A series of 6-alkylaminopurine arabinosides were synthesized and found to inhibit varicella-zoster virus (VZV). The antiviral activities of these nucleosides were limited to VZV. None of the other viruses tested in the herpesvirus family were affected. The in vitro antiviral potencies of the 18 arabinosides correlated with their efficiencies as substrates of the VZV-encoded thymidine kinase in all but one case. The arabinosides of 6-methylaminopurine and 6-dimethylaminopurine were the most potent analogs, with 50% inhibitory concentrations against VZV of 3 and 1 microM, respectively. They were not cytotoxic to uninfected MRC-5 cells, human Detroit 98 cells, or mouse L cells (50% inhibitory concentration, greater than 100 microM). Neither 6-methylaminopurine arabinoside nor 6-dimethylaminopurine arabinoside was detectably phosphorylated by either adenosine kinase or 2'-deoxycytidine kinase. These two alkylaminopurine arabinosides were also resistant to deamination catalyzed by adenosine deaminase. The VZV-dependent phosphorylation of these nucleosides offers the possibility of a potent and highly selective therapy for VZV infection.
- Subjects :
- Adenosine Deaminase Inhibitors
Animals
Antiviral Agents pharmacology
Chemical Phenomena
Chemistry, Physical
L Cells drug effects
Magnetic Resonance Spectroscopy
Mice
Phosphotransferases antagonists & inhibitors
Vidarabine chemical synthesis
Vidarabine pharmacology
Antiviral Agents chemical synthesis
Herpesvirus 3, Human drug effects
Vidarabine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0066-4804
- Volume :
- 35
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 1656862
- Full Text :
- https://doi.org/10.1128/AAC.35.7.1437