title: Design, synthesis and anti flaviviridae activity of N(6)-, 5',3'-O- and 5',2'-O-substituted adenine nucleoside analogs.
abstract: During a random screening of representative libraries of nucleoside analogues we discovered that the adenine derivatives FEVB28 and FEG118 were Flaviviridae inhibitors endowed with potency comparable, if not superior, to that of ribavirin. Those studies prompted us to design a new class of protected nucleoside analogs, reported herein, which displays interesting anti-bovine viral diarrhea virus (BVDV) activity and low cytotoxicity in cell-based assays (4, 23, 29 EC(50): 14, 11, 26 microM respectively, CC(50)>100 microM) and appreciable activity in enzyme assays against the RNA dependent RNA polymerase (RdRp) of BVDV (4, 23, 29, RdRp inhibition activity 27, 16, 15 microM respectively). A molecular modeling study was also carried out to highlight the possible interactions between this compounds class and the corresponding hepatitis C virus (HCV) enzyme.
authors: Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors: Angela
authors: A
authors: Angusti
authors: Stefano
authors: S
authors: Manfredini
authors: Elisa
authors: E
authors: Durini
authors: Nunzia
authors: N
authors: Ciliberti
authors: Silvia
authors: S
authors: Vertuani
authors: Nicola
authors: N
authors: Solaroli
authors: Sabrina
authors: S
authors: Pricl
authors: Marco
authors: M
authors: Ferrone
authors: Maurizio
authors: M
authors: Fermeglia
authors: Roberta
authors: R
authors: Loddo
authors: Barbara
authors: B
authors: Secci
authors: Anna
authors: A
authors: Visioli
authors: Tiziana
authors: T
authors: Sanna
authors: Gabriella
authors: G
authors: Collu
authors: Margherita
authors: M
authors: Pezzullo
authors: Paolo
authors: P
authors: La Colla
mesh_terms: D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002417:Cattle; D002460:Cell Line; D002855:Chromatography, Thin Layer; D003198:Computer Simulation; D006224:Cricetinae; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D019277:Entropy; D018067:Flaviviridae / Q000187:drug effects*; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007202:Indicators and Reagents; D013778:Tetrazolium Salts; D013844:Thiazoles; D012324:RNA-Dependent RNA Polymerase; C022616:thiazolyl blue