Autor(es): Nothias-Scaglia Louis-Félix, Pannecouque Christophe, Renucci Franck, Delang Leen, Neyts Johan, Roussi Fanny, Costa Jean, Leyssen Pieter, Litaudon Marc, Paolini Julien

Resumo: Recently, new daphnane, tigliane, - 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 - 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 ?M - 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 - HIV-2. Tigliane- (4?-hydroxyphorbol analogues 10, 11, 13, 15, 16, - 18) - ingenane-type (27 - 28) diterpene esters were shown to inhibit HIV replication in vitro at the nanomolar level. A Pearson analysis performed with the anti-CHIKV - anti-HIV data sets demonstrated a linear relationship, which supported the hypothesis made that PKC may be an important target in CHIKV replication.

Imprenta: Journal of Natural Products, v. 78, n. 6, p. 1277-1283, 2015

Identificador do objeto digital: 10.1021/acs.jnatprod.5b00073

Descritores: Chikungunya virus - DNA ; Chikungunya virus - Molecular structure ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus

Data de publicação: 2015

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