6-Azathymidine-4'-thionucleosides: synthesis and antiviral evaluation
Malina Jasamai1, Jan Balzarini, Claire Simons
1Medicinal Chemistry, Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, UK.
Abstract:
The synthesis of dideoxy-6-azathymidine 4'-thionucleoside 1-(2,3-dideoxy-4-thio-beta-D-erythro-pentofuranosyl)-(6-azathymidine) (2), and the L-nucleoside, 1-(4-thio-beta-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 microM) 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.
Related Concept Videos
Antiviral Nucleoside Inhibitors
Inhibitors of Viral Protein Synthesis
Antiprotozoal Agents
Inhibitors of Virion Maturation and Assembly
Inhibitors of Bacterial DNA Synthesis
Inhibitors Of Virion Release


