title: Synthesis and anti-hepatitis B virus and anti-hepatitis C virus activities of 7-deazaneplanocin A analogues in vitro.
abstract: A series of 7-deazaneplanocin A (7-DNPA, 2) analogues were synthesized and evaluated for in vitro antiviral activity against HBV and HCV. The syntheses of target carbocyclic nucleosides were accomplished via a convergent procedure. 7-Substitutions were introduced by using 7-substituted-7-deaza heterocyclic base precursors (F, Cl, Br, and I) or via substitution reactions after the synthesis of the carbocyclic nucleosides. Among the synthesized compounds, 2, 13-15, 24, and 27 exhibited significant anti-HCV activity (EC(50) ranged from 1.8 to 20.1 microM) and compounds 2, 15, 22, and 24 demonstrated moderate to potent anti-HBV activity (EC(50) = 0.3-3.3 microM). In addition, compound 24 also showed activity against lamivudine- and adefovir-associated HBV mutants.
authors.affiliation: The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA.
authors.forename: Hyo-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ashoke
authors.initials: A
authors.lastname: Sharon
authors.forename: Chandralata
authors.initials: C
authors.lastname: Bal
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.forename: Madhan
authors.initials: M
authors.lastname: Allu
authors.forename: Zhuhui
authors.initials: Z
authors.lastname: Huang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Murray
authors.forename: Leda
authors.initials: L
authors.lastname: Bassit
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.forename: Brent
authors.initials: B
authors.lastname: Korba
authors.forename: Chung K
authors.initials: CK
authors.lastname: Chu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
chemical_list: C508195:7-deazaneplanocin A; D000998:Antiviral Agents; D000241:Adenosine