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

Resumo: Bioassay-guided purification of an EtOAc extract of the whole plant of Euphorbia amygdaloides ssp. semiperfoliata using a chikungunya virus-cell-based assay led to the isolation of six new (1-4, 9, - 10) - six known (5-7, 8, 11, - 12) jatrophane esters. Their planar structures - relative configurations were determined by extensive spectroscopic analysis, - their absolute configurations by X-ray analysis. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, - HIV-1 - HIV-2 viruses. Compound 3 was found to be the most potent - selective inhibitor of the replication of CHIKV - of HIV-1 - HIV-2 (EC50 = 0.76, IC50 = 0.34 - 0.043 ?M, respectively). A preliminary structure-activity relationship study demonstrated that potency - selectivity are very sensitive to the substitution pattern on the jatrophane skeleton. Although replication strategies of CHIK - HIV viruses are quite different, the mechanism of action by which these compounds act may involve a similar target for both viruses. The present results provide additional support for a previous hypothesis that the anti-CHIKV activity could involve a PKC-dependent mechanism.

Imprenta: Journal of Natural Products, v. 77, n. 6, p. 1505-1512, 2014

Identificador do Objeto Digital: 10.1021/np500271u

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever

Data de Publicação: 2014