title: Depsides: lichen metabolites active against hepatitis C virus.
abstract: A thorough phytochemical study of Stereocaulon evolutum was conducted, for the isolation of structurally related atranorin derivatives. Indeed, pilot experiments suggested that atranorin (1), the main metabolite of this lichen, would interfere with the lifecycle of hepatitis C virus (HCV). Eight compounds, including one reported for the first time (2), were isolated and characterized. Two analogs (5, 6) were also synthesized, to enlarge the panel of atranorin-related structures. Most of these compounds were active against HCV, with a half-maximal inhibitory concentration of about 10 to 70 µM, with depsides more potent than monoaromatic phenols. The most effective inhibitors (1, 5 and 6) were then added at different steps of the HCV lifecycle. Interestingly, atranorin (1), bearing an aldehyde function at C-3, inhibited only viral entry, whereas the synthetic compounds 5 and 6, bearing a hydroxymethyl and a methyl function, respectively, at C-3 interfered with viral replication.
authors: CNRS, UMR-6226, Institut des Sciences Chimiques de Rennes (ISCR), Rennes, France; Université de Rennes 1, Rennes, France.
authors: Thi Huyen
authors: TH
authors: Vu
authors: CNRS, UMR-6226, Institut des Sciences Chimiques de Rennes (ISCR), Rennes, France; Université de Rennes 1, Rennes, France; Université de Toulouse III, Toulouse, France.
authors: Anne-Cécile
authors: AC
authors: Le Lamer
authors: CNRS, UMR-6226, Institut des Sciences Chimiques de Rennes (ISCR), Rennes, France; Université de Rennes 1, Rennes, France.
authors: Claudia
authors: C
authors: Lalli
authors: CNRS, UMR-6226, Institut des Sciences Chimiques de Rennes (ISCR), Rennes, France; Université de Rennes 1, Rennes, France.
authors: Joël
authors: J
authors: Boustie
authors: Université de Rennes 1, Rennes, France; INSERM, UMR-1085, Institut de Recherche Santé Environnement & Travail (IRSET), Rennes, France; Fédération de Recherche BioSit de Rennes, Rennes, France.
authors: Michel
authors: M
authors: Samson
authors: CNRS, UMR-6226, Institut des Sciences Chimiques de Rennes (ISCR), Rennes, France; Université de Rennes 1, Rennes, France.
authors: Françoise
authors: F
authors: Lohézic-Le Dévéhat
authors: Université de Rennes 1, Rennes, France; INSERM, UMR-1085, Institut de Recherche Santé Environnement & Travail (IRSET), Rennes, France; Fédération de Recherche BioSit de Rennes, Rennes, France.
authors: Jacques
authors: J
authors: Le Seyec
mesh_terms: D053630:Depsides / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D062385:Hydroxybenzoates / Q000737:chemistry; D008011:Lichens / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D053630:Depsides; D062385:Hydroxybenzoates; C026304:atranorin