title: LC-MS²-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity.
abstract: Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent and selective antiviral activity on the replication of Chikungunya virus (CHIKV) in cell culture. With the objective to found new compounds with anti-CHIKV activities, 45 extracts from various plant parts of 11 Mediterranean Euphorbia and one Mercurialis species were evaluated for selective inhibition of CHIKV replication. All EtOAc extracts, especially those prepared from latex, exhibited significant and selective antiviral activity in a Chikungunya virus-cell-based assay. An LC-MS(2) dereplication method was then developed to investigate whether known diterpenoids with anti-CHIKV activity, such as the potent anti-CHIKV 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-didecanoate, and prostratin as well as 24 other commercially available diterpenoids of tigliane-, ingenane-, and daphnane-type for which the anti-CHIKV activity have been established in advance (Nothias-Scaglia et al. 2015), were present in the Euphorbia extracts. Only ingenol-3-mebutate, 13-O-isobutyryl-12-deoxyphorbol-20-acetate, and ingenol-3,20-dibenzoate, all exhibiting weak anti-CHIKV activities, were detected in the EtOAc extracts of Euphorbia peplus, Euphorbia segetalis ssp. pinea, and Euphorbia pithyusa ssp. pithyusa. Given the potent anti-CHIKV activities of these Euphorbia extracts, the present study suggested that their antiviral activities are probably due to untargeted diterpenoids.
authors.affiliation: Laboratoire de Chimie de Produits Naturels, UMR CNRS SPE 6134, University of Corsica, 20250 Corte, France; Institut de Chimie des Substances Naturelles ICSN-CNRS UPR 2301, Univ. Paris-Sud, 1 avenue de la terrasse, Labex CEBA, 91198 Gif-sur-Yvette, France.
authors.forename: Louis-Félix
authors.initials: LF
authors.lastname: Nothias-Scaglia
authors.affiliation: Institut de Chimie des Substances Naturelles ICSN-CNRS UPR 2301, Univ. Paris-Sud, 1 avenue de la terrasse, Labex CEBA, 91198 Gif-sur-Yvette, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dumontet
authors.affiliation: Laboratory for Virology and Experimental 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 ICSN-CNRS UPR 2301, Univ. Paris-Sud, 1 avenue de la terrasse, Labex CEBA, 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 Experimental 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 ICSN-CNRS UPR 2301, Univ. Paris-Sud, 1 avenue de la terrasse, Labex CEBA, 91198 Gif-sur-Yvette, France. Electronic address: marc.litaudon@cnrs.fr.
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. Electronic address: paolini@univ-corse.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Paolini
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000302:isolation & purification; D002646:Chikungunya virus / Q000187:drug effects* / Q000502:physiology; D002522:Chlorocebus aethiops; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification; D028481:Euphorbia / Q000737:chemistry*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; D010936:Plant Extracts
keywords: 12-Deoxyphorbol-13-acetate (PubChem CID:45217); 12-O-Tetradecanoylphorbol-13-acetate (PubChem CID:27924); Antiviral activity; Chikungunya virus; Diterpene esters; Euphorbia; Ingenol-3,20-dibenzoate (PubChem: 442043); Ingenol-3-mebutate (PubChem CID:6918670); LC-MS(2); Phorbol-12,13-didecanoate (PubChem CID:71308620); Resiniferatoxin (PubChem CID:5702546)