RESUMEN

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.

Asunto(s)

Antivirales/química , Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Benzoxazoles/química , Benzoxazoles/farmacología , Relación Dosis-Respuesta a Droga , Hepacivirus/fisiología , Humanos , ARN Helicasas/antagonistas & inhibidores , ARN Helicasas/fisiología , Replicación Viral/fisiología