Nothias-Scaglia Louis-Félix, Pannecouque Christophe, Renucci Franck, Delang Leen, Neyts Johan, Roussi Fanny, Costa Jean, Leyssen Pieter, Litaudon Marc, Paolini Julien
†Laboratoire de Chimie de Produits Naturels, UMR CNRS SPE 6134, University of Corsica, 20250, Corte, France.
‡Institut de Chimie des Substances Naturelles CNRS-ICSN UPR 2301, University Paris-Sud, LabEx CEBA, 1 Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
J Nat Prod. 2015 Jun 26;78(6):1277-83. doi: 10.1021/acs.jnatprod.5b00073. Epub 2015 May 13.
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 ± 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 ± 0.1 μM and 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 and HIV-2. Tigliane- (4β-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.
最近，从各种大戟科植物中分离出了新的瑞香烷型、替告烷型和麻风树烷型二萜类化合物，其中一些已被证明是基孔肯雅病毒（CHIKV）复制的有效抑制剂。为了进一步探索这类化合物，评估了一系列29种市售天然二萜类化合物的抗病毒活性。佛波醇-12,13-二十二酸酯（11）被证明是最有效的抑制剂，其半数有效浓度（EC50）值为6.0±0.9 nM，选择性指数（SI）为686，这与先前报道的结构相关的12-O-十四烷酰佛波醇-13-乙酸酯（13）的抗CHIKV效力一致。大多数其他化合物表现出低至中等的活性，包括一种大戟烷型二萜酯化合物28，其EC50值为1.2±0.1 μM，SI = 6.4。已知二萜类化合物也能抑制HIV复制，因此还评估了化合物1-29对HIV-1和HIV-2的抗病毒活性。替告烷型（4β-羟基佛波醇类似物10、11、13、15、16和18）和大戟烷型（27和28）二萜酯在体外显示出在纳摩尔水平上抑制HIV复制。对抗CHIKV和抗HIV数据集进行的Pearson分析表明存在线性关系，这支持了蛋白激酶C（PKC）可能是CHIKV复制中的重要靶点这一假设。
