title: Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi.
abstract: In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and poliothrysoside, and betulinic acid 3β-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM).
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, LabEx LERMIT, 1, Avenue de la Terrasse, 91198 Gif sur Yvette Cedex, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bourjot
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.forename: Cécilia
authors.initials: C
authors.lastname: Eydoux
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Guillemot
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
authors.forename: Philippe
authors.initials: P
authors.lastname: Rasoanaivo
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéritte
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002646:Chikungunya virus / Q000187:drug effects; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003716:Dengue Virus / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008270:Madagascar; D019906:Nuclear Magnetic Resonance, Biomolecular; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry; D031308:Salicaceae / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006027:Glycosides; D010636:Phenols; C573605:flacourtoside F; D012321:DNA-Directed RNA Polymerases