With the aim of identifying novel lead compounds active against emergent human infectious diseases, a series of 2,3-dihydro-4H-pyridinone derivatives has been prepared and evaluated for antiviral activity. Compounds were evaluated in vitro in cell-based assays for cytotoxicity and against a wide spectrum of viruses. In the antiviral screening, several compounds showed to be fairly active against viruses belonging to the Flaviviridae family. The Pestiviruses (bovine viral diarrhoea virus) were inhibited by 4acis (CC(50) > 100 mu m; EC(50) = 14 mu m), compounds 4ccis and 6a showed a significant activity against Flaviviruses (Yellow Fever Virus) (CC(50) > 100 mu m; EC(50) = 18 mu m, CC(50) > 100 mu m; EC(50) = 10 mu m). Among these, compound 6a displayed great inhibitory activity against Hepaciviruses (hepatitis C virus) in replicon assay [CC(50) > 100 mu m; EC(50)(1b) = 4 mu m]. In vitro inhibitory activity against the HCV RNA-dependent RNA polymerase (NS5B) of title compounds is discussed. The antiviral screening of viral strains indicated that compound 6a can be selected as promising tool in novel anti-flaviviruses development.

2,3-Dihydro-1,2-Diphenyl-substituted 4HPyridinone Derivatives as New Anti Flaviviridae Inhibitors

PEDUTO, ANTONELLA;MASSA, Antonio;DI MOLA, ANTONIA;DE CAPRARIIS, Paolo;FILOSA, Rosanna
2011

Abstract

With the aim of identifying novel lead compounds active against emergent human infectious diseases, a series of 2,3-dihydro-4H-pyridinone derivatives has been prepared and evaluated for antiviral activity. Compounds were evaluated in vitro in cell-based assays for cytotoxicity and against a wide spectrum of viruses. In the antiviral screening, several compounds showed to be fairly active against viruses belonging to the Flaviviridae family. The Pestiviruses (bovine viral diarrhoea virus) were inhibited by 4acis (CC(50) > 100 mu m; EC(50) = 14 mu m), compounds 4ccis and 6a showed a significant activity against Flaviviruses (Yellow Fever Virus) (CC(50) > 100 mu m; EC(50) = 18 mu m, CC(50) > 100 mu m; EC(50) = 10 mu m). Among these, compound 6a displayed great inhibitory activity against Hepaciviruses (hepatitis C virus) in replicon assay [CC(50) > 100 mu m; EC(50)(1b) = 4 mu m]. In vitro inhibitory activity against the HCV RNA-dependent RNA polymerase (NS5B) of title compounds is discussed. The antiviral screening of viral strains indicated that compound 6a can be selected as promising tool in novel anti-flaviviruses development.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/3040678
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