title: 2,3-Dihydro-1,2-Diphenyl-substituted 4H-Pyridinone derivatives as new anti Flaviviridae inhibitors.
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 4a cis (CC(50) > 100 μm; EC(50) = 14 μm), compounds 4c cis and 6a showed a significant activity against Flaviviruses (Yellow Fever Virus) (CC(50) > 100 μm; EC(50) = 18μm, CC(50) > 100 μm; EC(50) = 10 μm). Among these, compound 6a displayed great inhibitory activity against Hepaciviruses (hepatitis C virus) in replicon assay [CC(50) > 100 μm; EC(50) (1b) = 4 μm]. 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.
authors.affiliation: Dipartimento di Chimica, Università di Salerno, Italy Dipartimento di Scienze Farmaceutiche, Università di Salerno, 84084 Fisciano (SA), Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Peduto
authors.forename: Antonio
authors.initials: A
authors.lastname: Massa
authors.forename: Antonia
authors.initials: A
authors.lastname: Di Mola
authors.forename: Paolo
authors.initials: P
authors.lastname: de Caprariis
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
authors.forename: Sergio
authors.initials: S
authors.lastname: Altamura
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Rosanna
authors.initials: R
authors.lastname: Filosa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D018067:Flaviviridae / Q000187:drug effects*; D018178:Flaviviridae Infections / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D011728:Pyridones