Antiviral Activity of Diterpene Esters on Chikungunya Virus and HIV Replication

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• 作者：Louis-F茅lix Nothias-Scaglia ; Christophe Pannecouque ; Franck Renucci ; Leen Delang ; Johan Neyts ; Fanny Roussi ; Jean Costa ; Pieter Leyssen ; Marc Litaudon ; Julien Paolini
• 刊名：Journal of Natural Products
• 出版年：2015
• 出版时间：June 26, 2015
• 年：2015
• 卷：78
• 期：6
• 页码：1277-1283
• 全文大小：342K
• ISSN：1520-6025

文摘

Recently, new daphnane, tigliane, and 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 卤 0.9 nM and 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 卤 0.1 渭M and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so the antiviral activities of compounds 1鈥?b>29 were evaluated also against HIV-1 and HIV-2. Tigliane- (4尾-hydroxyphorbol analogues 10, 11, 13, 15, 16, and 18) and ingenane-type (27 and 28) diterpene esters were shown to inhibit HIV replication in vitro at the nanomolar level. A Pearson analysis performed with the anti-CHIKV and anti-HIV data sets demonstrated a linear relationship, which supported the hypothesis made that PKC may be an important target in CHIKV replication.