title: Alkylated flavanones from the bark of Cryptocarya chartacea as dengue virus NS5 polymerase inhibitors.
abstract: 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 IC(50) ranging from 1.8 to 4.2 μM. Chartaceones represent a new class of non-nucleosidic inhibitors of the DENV NS5 RdRp.
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors: Pierre-Marie
authors: PM
authors: Allard
authors: Elise Tran Huu
authors: ET
authors: Dau
authors: Cécilia
authors: C
authors: Eydoux
authors: Jean-Claude
authors: JC
authors: Guillemot
authors: Vincent
authors: V
authors: Dumontet
authors: Cyril
authors: C
authors: Poullain
authors: Bruno
authors: B
authors: Canard
authors: Françoise
authors: F
authors: Guéritte
authors: Marc
authors: M
authors: Litaudon
mesh_terms: D000478:Alkylation; D031369:Cryptocarya / Q000737:chemistry*; D003716:Dengue Virus / Q000187:drug effects* / Q000201:enzymology; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005602:France; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
chemical_list: D044950:Flavanones; C016063:pinocembrin; D012324:RNA-Dependent RNA Polymerase