Antiviral agents. 1-Aralkyloxyadenosines

Wm, Shannon; Shortnacy, Anita T.; Arnett, G.; Ja, Montgomery

doi:10.1021/jm00249a025

Cited by 14 publications

(2 citation statements)

References 1 publication

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…structures were recently summarized in reviews by De Clercq 1 , Baker et al 2 , and Smee et al 3 Of the tested compounds, adenosine N 1 -oxide (1) and some of its N 1 -benzyloxy derivatives were shown to exhibit a significant activity against vaccinia virus in a cell culture assay and in a mouse model of vaccinia-virus-induced tailpox lesion [4][5][6] . Kane and Shuman 7 showed that adenosine N 1 -oxide inhibits vaccinia virus replication in vitro by selectively blocking the translation of viral mRNA, although the mechanism was undetermined.…”

mentioning

confidence: 99%

Adenosine N1-Oxide Analogues as Inhibitors of Orthopox Virus Replication

Khandazhinskaya

Shirokova

Shipitsin

et al. 2006

Collect. Czech. Chem. Commun.

View full text Add to dashboard Cite

Several new types of adenosine N 1 -oxide (ANO) derivatives including N 1 -alkoxy and N 6 -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 N 6 -position did not offer any advantages over the parent compound. The synthesized N 1 -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.

show abstract

mentioning

confidence: 99%

Adenosine N1-Oxide Analogues as Inhibitors of Orthopox Virus Replication

Khandazhinskaya

Shirokova

Shipitsin

et al. 2006

Collect. Czech. Chem. Commun.

View full text Add to dashboard Cite

show abstract

“…Adenosine N 1 -oxide (ANO) is a highly selective inhibitor of vaccinia virus replication (22). ANO and an extensive series of 1-benzyloxy derivatives display a very high therapeutic index against vaccinia virus in cultured VERO cells, as determined by a reduction in cytopathic effect (22,34). These compounds were essentially inactive against any other viruses tested in cell culture (which included representative adeno-, flavi-, arena-, alpha-, phlebo-, and retroviruses).…”

mentioning

confidence: 99%

Adenosine N1-oxide inhibits vaccinia virus replication by blocking translation of viral early mRNAs

Kane

Shuman

1995

J Virol

View full text Add to dashboard Cite

Adenosine N 1 -oxide (ANO) is a potent and highly selective inhibitor of vaccinia virus replication. We examined the impact of ANO on vaccinia virus macromolecular synthesis during synchronous infection of BSC40 cells. Viral DNA replication and viral late protein synthesis were blocked completely by ANO, effects that were attributable to a defect in the expression of viral early genes. Vaccinia virus early proteins were not synthesized in the presence of ANO, even though vaccinia virus early mRNAs were produced. Cellular protein synthesis was unaffected by ANO, and virus infection in the presence of the drug did not elicit the normal shutoff of host protein synthesis. Adenosine N 1 -oxide triphosphate (ANO-TP), the predominant metabolite of the drug in vivo, could substitute for ATP in RNA synthesis by purified vaccinia virus RNA polymerase. ANO-TP could support early transcription by purified virions if dATP was provided as an energy source. ANO-TP did not inhibit early transcription in the presence of ATP. These findings suggest a novel antiviral mechanism whereby incorporation of a modified nucleotide into viral mRNAs might selectively block viral gene expression at the level of translation. We believe that ANO merits consideration as an antipoxvirus drug for topical treatment of molluscum contagiosum in humans.

show abstract