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UK-1 and structural analogs are potent inhibitors of hepatitis C virus replication. 2014
Dawn N Ward, and
Daniel C Talley, and
Mrinalini Tavag, and
Samrawit Menji, and
Paul Schaughency, and
Andrea Baier, and
Paul J Smith
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
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.
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