title: Prostratin and 12-O-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of Chikungunya virus replication.
abstract: A chemical study of the Vietnamese plant species Trigonostemon howii led to the isolation of a new tigliane-type diterpenoid, trigowiin A (1), along with several known coumarins and phenylpropanoids. The planar structure and the relative configuration of compound 1 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Trigowiin A (1) exhibited moderate antiviral activity in a virus-cell-based assay for Chikungunya virus (CHIKV). Since the structure of compound 1 is closely related to those of well-known tigliane diterpenoids such as prostratin (2), phorbol (3), 12-O-tetradecanoylphorbol 13-acetate (TPA) (4), and 4α-TPA (5), the antiviral activity of the latter compounds was also evaluated against CHIKV, as well as in virus-cell-based assays of two additional members of the genus Alphavirus (Sindbis virus, SINV, and Semliki forest virus, SFV). Whereas prostratin inhibited CHIKV replication with a moderate EC(50) of 2.6 μM and a selectivity index (SI) approximating 30, compound 4 proved to be an extremely potent inhibitor, with an EC(50) of ∼3 nM and a SI near 2000. Interestingly, no or very little activity was observed on the replication of SINV and SFV.
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: Leen
authors.initials: L
authors.lastname: Delang
authors.forename: Van Hung
authors.initials: VH
authors.lastname: Nguyen
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéritte
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
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*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019665:Euphorbiaceae / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010703:Phorbol Esters / Q000737:chemistry / Q000494:pharmacology*; D024301:Plant Bark / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014744:Vietnam
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; D010703:Phorbol Esters; C578640:trigowiin A; C070999:prostratin; D013755:Tetradecanoylphorbol Acetate