6-Azathymidine-4′-thionucleosides

Synthesis and antiviral evaluation

Malina Jasamai, Jan Balzarini, Claire Simons

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The synthesis of dideoxy-6-azathymidine 4′-thionucleoside 1-(2,3-dideoxy-4-thio-β-D-erythro-pentofuranosyl)-(6-azathymidine) (2), and the L-nucleoside, 1-(4-thio-β-L-erythro-pentofuranosyl)- (6-azathymidine) (3) and their evaluation against a wide panel of antiviral assays are described. The L-thionucleoside (3) was devoid of antiviral activity. The dideoxy-thionucleoside (2) was moderately active against vaccinia virus (VV) and the herpes simplex virus strains HSV-1 (strain KOS) and HSV-2 (strain G) (MIC 12 μM) and retained inhibitory activity vs a thymidine kinase-deficient strain HSV-1/TK-, suggesting that (2) is not dependent on viral TK-catalysed phosphorylation for antiviral activity and/or may use an alternative metabolic activation pathway.

Original languageEnglish
Pages (from-to)56-61
Number of pages6
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume23
Issue number1
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

Fingerprint

Thionucleosides
Antiviral Agents
Human Herpesvirus 1
Viruses
Human Herpesvirus 2
Thymidine Kinase
Vaccinia virus
Simplexvirus
Metabolic Networks and Pathways
Nucleosides
Phosphorylation
Assays
Chemical activation

Keywords

  • 6-Azathymidine-4′-thionucleosides
  • Antiviral
  • Dideoxynucleoside
  • L-nucleoside
  • Thymidine kinase deficient (TK-)

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

6-Azathymidine-4′-thionucleosides : Synthesis and antiviral evaluation. / Jasamai, Malina; Balzarini, Jan; Simons, Claire.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 23, No. 1, 02.2008, p. 56-61.

Research output: Contribution to journalArticle

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