Macrocyclic Diterpenoids from Euphorbia helioscopia and Their Potential Anti-inflammatory Activity
Macrocyclic Diterpenoids from Euphorbia helioscopia and Their Potential Anti-inflammatory Activity
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大戟中的大环二萜及其潜在的抗炎活性
DOI：
10.1021/acs.jnatprod.9b00519
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发表时间：
2019-10-01
影响因子：
5.1
通讯作者：
Wang, Ying
中科院分区：
文献类型：
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作者：
Su, Jun-Cheng;Cheng, Wen;Wang, Ying
以芳香族质子为探针，通过核磁共振氢谱实验，从泽漆地上部分分离得到11个大环二萜化合物。它们的完整三维结构，包括绝对构型，通过光谱分析和单晶X射线晶体学实验明确地建立。其中化合物1是迄今为止发现的第三个具有罕见的5/10稠环结构的大戟二萜类化合物，化合物2-4是新的麻风树烷型二萜。基于本研究中得到的Jatrophane二萜的NMR数据以及文献报道的晶体结构，考虑了相关碳的化学位移与其柔性大环的C-2，C-13和C-14构型的相关性。此外，通过监测1-11对脂多糖刺激的RAW 264.7细胞中一氧化氮产生的抑制作用来研究1-11的抗炎活性。化合物1显示出7.4 +/-0.6 μ M的IC 50，这可能与通过抑制p65亚基的易位和随后的IL-6和TNF-α分泌的减少来调节NF-κ B信号传导途径有关。
Guided by H-1 NMR spectroscopic experiments using the aromatic protons as probes, 11 macrocyclic diterpenes (111) were isolated from the aerial parts of Euphorbia helioscopia. Their full three-dimensional structures, including absolute configurations, were established unambiguously by spectroscopic analysis and single-crystal X-ray crystallographic experiments. Among the isolated compounds, compound 1 is the third member thus far of a rare class of Euphorbia diterpenes featuring an unusual 5/10 fused ring system, and 2-4 are new jatrophane diterpenes. Based on the NMR data of the jatrophane diterpenes obtained in this study as well as those with crystallographic structures reported in the literature, the correlations of the chemical shifts of the relevant carbons and the configurations of C-2, C-13, and C-14 of their flexible macrocyclic ring were considered. Moreover, the anti-inflammatory activities of 1-11 were investigated by monitoring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Compound 1 showed an IC50 of 7.4 +/- 0.6 mu M, which might be related to the regulation of the NF-kappa B signaling pathway by suppressing the translocation of the p65 subunit and the consequent reduction of IL-6 and TNF-alpha secretions.