title: Antiviral Activity of Diterpene Esters on Chikungunya Virus and HIV Replication.
abstract: Recently, new daphnane, tigliane, and jatrophane diterpenoids have been isolated from various Euphorbiaceae species, of which some have been shown to be potent inhibitors of chikungunya virus (CHIKV) replication. To further explore this type of compound, the antiviral activity of a series of 29 commercially available natural diterpenoids was evaluated. Phorbol-12,13-didecanoate (11) proved to be the most potent inhibitor, with an EC50 value of 6.0 ± 0.9 nM and a selectivity index (SI) of 686, which is in line with the previously reported anti-CHIKV potency for the structurally related 12-O-tetradecanoylphorbol-13-acetate (13). Most of the other compounds exhibited low to moderate activity, including an ingenane-type diterpene ester, compound 28, with an EC50 value of 1.2 ± 0.1 μM and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so the antiviral activities of compounds 1-29 were evaluated also against HIV-1 and HIV-2. Tigliane- (4β-hydroxyphorbol analogues 10, 11, 13, 15, 16, and 18) and ingenane-type (27 and 28) diterpene esters were shown to inhibit HIV replication in vitro at the nanomolar level. A Pearson analysis performed with the anti-CHIKV and anti-HIV data sets demonstrated a linear relationship, which supported the hypothesis made that PKC may be an important target in CHIKV replication.
authors.affiliation: †Laboratoire de Chimie de Produits Naturels, UMR CNRS SPE 6134, University of Corsica, 20250, Corte, France.|‡Institut de Chimie des Substances Naturelles CNRS-ICSN UPR 2301, University Paris-Sud, LabEx CEBA, 1 Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors.forename: Louis-Félix
authors.initials: LF
authors.lastname: Nothias-Scaglia
authors.affiliation: §Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.affiliation: †Laboratoire de Chimie de Produits Naturels, UMR CNRS SPE 6134, University of Corsica, 20250, Corte, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Renucci
authors.affiliation: §Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Delang
authors.affiliation: §Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: ‡Institut de Chimie des Substances Naturelles CNRS-ICSN UPR 2301, University Paris-Sud, LabEx CEBA, 1 Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Roussi
authors.affiliation: †Laboratoire de Chimie de Produits Naturels, UMR CNRS SPE 6134, University of Corsica, 20250, Corte, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Costa
authors.affiliation: §Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: ‡Institut de Chimie des Substances Naturelles CNRS-ICSN UPR 2301, University Paris-Sud, LabEx CEBA, 1 Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
authors.affiliation: †Laboratoire de Chimie de Produits Naturels, UMR CNRS SPE 6134, University of Corsica, 20250, Corte, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Paolini
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002646:Chikungunya virus / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004952:Esters; D019665:Euphorbiaceae / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D015394:Molecular Structure; D010703:Phorbol Esters / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004224:Diterpenes; D004952:Esters; D010703:Phorbol Esters; C530110:ingenane; C530345:jatrophane; C008876:phorbol-12,13-didecanoate; C011309:mezerein; D013755:Tetradecanoylphorbol Acetate