Document Report Card

ID: ALA1138495

Journal: J Med Chem

Title: Inhibition of subgenomic hepatitis C virus RNA replication by acridone derivatives: identification of an NS3 helicase inhibitor.

Authors: Manfroni G, Paeshuyse J, Massari S, Zanoli S, Gatto B, Maga G, Tabarrini O, Cecchetti V, Fravolini A, Neyts J.

Abstract: We report the synthesis and structure-activity relationship (SAR) of a large series of acridones and acridone-fragment derivatives designed on the basis of the selective antihepatitis C virus (HCV) activity shown by acridone 2, previously studied as a potential antibovine viral diarrhea virus (BVDV) compound. The evaluation of their ability to inhibit the HCV replication in Huh-5-2 cells led to the identification of new, selective inhibitors. This indicates that the acridone skeleton, when properly functionalized, is a suitable scaffold to obtain potential anti-HCV agents. Interestingly, during identification of possible cellular and viral targets, it was discovered that compound 23 exerts inhibitory activity on the HCV NS3 helicase, a very promising target for the development of anti-HCV drugs.

CiteXplore: 19388645

DOI: 10.1021/jm801608u