Autor(es): Olivon Florent, Palenzuela Héliciane, Girard-Valenciennes Emmanuelle, Neyts Johan, Pannecouque Christophe, Roussi Fanny, Grondin Isabelle, Leyssen Pieter, Litaudon Marc

Resumo: In an effort to identify new potent - selective inhibitors of chikungunya virus - HIV-1 - HIV-2 virus replication, the endemic Mascarene species Stillingia lineata was investigated. LC/MS - bioassay-guided purification of the EtOAc leaf extract using a chikungunya virus-cell-based assay led to the isolation of six new (4-9) - three known (1-3) tonantzitlolones possessing the rare C20-flexibilane skeleton, along with tonantzitloic acid (10), a new linear diterpenoid, - three new (11, 13, - 15) - two known (12 - 14) tigliane-type diterpenoids. The planar structures of the new compounds - their relative configurations were determined by spectroscopic analysis, - their absolute configurations were determined through comparison with literature data - from biogenetic considerations. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, -, for compounds 11-15, the HIV-1 - HIV-2 viruses. Compounds 12-15 were found to be the most potent - are selective inhibitors of CHIKV, HIV-1, - HIV-2 replication. In particular, compound 14 inhibited CHIKV replication with an EC50 value of 1.2 ?M on CHIKV - a selectivity index of >240, while compound 15 inhibited HIV-1 - HIV-2 with EC50 values of 0.043 - 0.018 ?M, respectively. It was demonstrated further that potency - selectivity are sensitive to the substitution pattern on the tigliane skeleton. The cytotoxic activities of compounds 1-10 were evaluated against the HCT-116, MCF-7, - PC3 cancer cell lines.

Imprenta: Journal of Natural Products, v. 78, n. 5, p. 1119-1128, 2015

Identificador do objeto digital: 10.1021/acs.jnatprod.5b00116

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

Data de publicação: 2015

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