jm801608u_si_001.pdf (170.68 kB)

Inhibition of Subgenomic Hepatitis C Virus RNA Replication by Acridone Derivatives: Identification of an NS3 Helicase Inhibitor

Download (170.68 kB)
journal contribution
posted on 28.05.2009, 00:00 by Giuseppe Manfroni, Jan Paeshuyse, Serena Massari, Samantha Zanoli, Barbara Gatto, Giovanni Maga, Oriana Tabarrini, Violetta Cecchetti, Arnaldo Fravolini, Johan Neyts
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.