title: UK-1 and structural analogs are potent inhibitors of hepatitis C virus replication.
abstract: The bacterial natural product UK-1 and several structural analogs inhibit replication of the hepatitis C virus in the replicon assay, with IC50 values as low as 0.50 μM. The NS3 helicase has been identified as a possible target of inhibition for several of these compounds, while the remaining inhibitors act via an undetermined mechanism. Gel shift assays suggest that helicase inhibition is a direct result of inhibitor-enzyme binding as opposed to direct RNA binding, and the ATPase activity of NS3 is not affected. The syntheses and biological results are presented herein.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
authors.forename: Dawn N
authors.initials: DN
authors.lastname: Ward
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Talley
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Tavag
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
authors.forename: Samrawit
authors.initials: S
authors.lastname: Menji
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Schaughency
authors.affiliation: Department of Molecular Biology, John Paul II Catholic University of Lublin, Poland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baier
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States. Electronic address: pjsmith@umbc.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Smith
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001583:Benzoxazoles / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D001583:Benzoxazoles; C082787:UK 1; D020365:RNA Helicases
keywords: Helicase; Hepatitis C; Inhibitor; NS3