Alkylated Flavanones from the Bark of Cryptocarya chartacea As Dengue Virus NS5 Polymerase Inhibitors

An in vitro screening of New Caledonian plants allowed the selection of several species with a significant dengue virus NS5 RNA-dependent RNA polymerase (RdRp) inhibiting activity. The chemical investigation of Cryptocarya chartacea led to the isolation of a series of new mono- and dialkylated flavanones named chartaceones A-F (1-6), along with pinocembrin. They were isolated as racemic mixtures and characterized using extensive one- and two-dimensional NMR spectroscopy. Four diastereomers of chartaceone A (1) were separated using chiral HPLC, and their absolute configurations were established by comparison of their experimental and calculated ECD spectra. The dialkylated flavanones, chartaceones C-F (3-6), exhibited the most significant NS5 RdRp inhibiting activity, with IC50 ranging from 1.8 to 4.2 mu M. Chartaceones represent a new class of non-nucleosidic inhibitors of the DENV NS5 RdRp.