LC-MS²-based dereplication of euphorbia extracts with anti-Chikungunya virus activity

Autor(es): Nothias-Scaglia Louis-Félix, Dumontet Vincent, Neyts Johan, Roussi Fanny, Costa Jean, Leyssen Pieter, Litaudon Marc, Paolini Julien


Resumo: Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent - 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 - one Mercurialis species were evaluated for selective inhibition of CHIKV replication. All EtOAc extracts, especially those prepared from latex, exhibited significant - 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, - prostratin as well as 24 other commercially available diterpenoids of tigliane-, ingenane-, - 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, - ingenol-3,20-dibenzoate, all exhibiting weak anti-CHIKV activities, were detected in the EtOAc extracts of Euphorbia peplus, Euphorbia segetalis ssp. pinea, - 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.


Palavras-Chave: 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)


Imprenta: Fitoterapia, v. 105, p. 202-209, 2015


Identificador do objeto digital: 10.1016/j.fitote.2015.06.021


Descritores: Chikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya Virus - Virus


Data de publicação: 2015