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Synthesis of beta-enantiomers of N4-hydroxy-3'-deoxypyrimidine nucleosides and their evaluation against bovine viral diarrhoea virus and hepatitis C virus in cell culture.
Antivir Chem Chemother ; 15(1): 43-55, 2004 Jan.
Article en En | MEDLINE | ID: mdl-15074714
N4-Hydroxycytidine (NHC) was recently reported to have anti-pestivirus and anti-hepacivirus activity. It is thought that this nucleoside acts as a weak alternative substrate for the hepatitis C virus (HCV) polymerase. In addition to NHC, 3'-deoxyuridine (3'-dU) was found to inhibit bovine diarrhoea virus (BVDV) production by 1 log10 at 37.2 microM. These initial findings prompted the synthesis of beta-D and beta-L analogues of (i) base-modified 3'-deoxy-NHC; (ii) 3'-deoxyuridine; and 3'-deoxycytidine. The antiviral activity of these 42 nucleosides was evaluated against BVDV and HCV bicistronic replicon in cell culture. Among the NHC analogues, the antiviral activity observed for the beta-L-3'-deoxy-5-fluoro-derivative 1-(3-deoxy-beta-L-erythro-pentofuranosyl)-5-fluoro-4-hydroxyaminopyrimidin-2(1H)-one and the beta-D-3'-deoxy-5-iodo-derivative 1-(3-deoxy-beta-D-erythro-pentofuranosyl)-5-iodocytosine in the replicon system (1 log10 reduction at 100 microM) was due to the concomitant toxicity towards intracellular ribosomal RNA levels (CC90 equal or lower than the EC90). In conclusion, none of the newly synthesized derivatives exhibited enhanced antiviral activity compared to the parent nucleoside NHC.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Nucleósidos de Pirimidina / Virus de la Diarrea Viral Bovina / Hepacivirus Límite: Animals Idioma: En Revista: Antivir Chem Chemother Asunto de la revista: QUIMICA / TERAPIA POR MEDICAMENTOS / VIROLOGIA Año: 2004 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Nucleósidos de Pirimidina / Virus de la Diarrea Viral Bovina / Hepacivirus Límite: Animals Idioma: En Revista: Antivir Chem Chemother Asunto de la revista: QUIMICA / TERAPIA POR MEDICAMENTOS / VIROLOGIA Año: 2004 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido