Collect. Czech. Chem. Commun. 2006, 71, 1107-1121

Adenosine N1-Oxide Analogues as Inhibitors of Orthopox Virus Replication

Anastasiya L. Khandazhinskayaa, Elena A. Shirokovaa, Alexander V. Shipitsina, Inna L. Karpenkoa, Evgenii F. Belanovb, Marina K. Kukhanovaa and Maksim V. Yaskoa,*

a Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov Str., Moscow 119991, Russian Federation
b State Research Center of Virology and Biotechnology "Vektor", Koltsovo, Novosibirsk Region 633159, Russian Federation


Several new types of adenosine N1-oxide (ANO) derivatives including N1-alkoxy and N6-alkyl as well as the analogues with a trihydroxycyclopentane ring in place of the ribose residue were synthesized and their antiviral properties were evaluated in Vero and LLC-MK2 cell cultures infected with vaccinia, mousepox, monkeypox, cowpox, and different isolates of smallpox viruses. The antiviral activity of ANO and its derivatives significantly depended on the virus type and cell cultures. Mousepox and monkeypox viruses were the most sensitive to these compounds, while vaccinia and cowpox viruses were inhibited at the concentrations 1-1.5 orders of magnitude higher. The toxicity of the synthesized compounds was much lower than that of ANO. Modifications of the ANO N6-position did not offer any advantages over the parent compound. The synthesized N1-oxide derivatives of noraristeromycin retained the activity comparable with noraristeromycin and displayed a decreased toxicity. No direct correlation between antiviral activity and stability of the compounds was found.

Keywords: Nucleosides; Purines; N-Oxides; Carbocyclic nucleosides; Noraristeromycin; Antivirals; Pox viruses.

References: 14 live references.