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Environmentally Friendly Procedure Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking for the Discovery of Potent Antiviral Compounds from Euphorbia semiperfoliata
Journal of Natural Products ( IF 5.1 ) Pub Date : 2017-09-19 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00113 Louis-Félix Nothias 1, 2, 3, 4 , Stéphanie Boutet-Mercey 1 , Xavier Cachet 1, 5 , Erick De La Torre 6, 7 , Laurent Laboureur 1 , Jean-François Gallard 1 , Pascal Retailleau 1 , Alain Brunelle 1 , Pieter C. Dorrestein 3, 4 , Jean Costa 2 , Luis M. Bedoya 6, 7 , Fanny Roussi 1 , Pieter Leyssen 8 , José Alcami 6, 7 , Julien Paolini 2 , Marc Litaudon 1 , David Touboul 1
Journal of Natural Products ( IF 5.1 ) Pub Date : 2017-09-19 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00113 Louis-Félix Nothias 1, 2, 3, 4 , Stéphanie Boutet-Mercey 1 , Xavier Cachet 1, 5 , Erick De La Torre 6, 7 , Laurent Laboureur 1 , Jean-François Gallard 1 , Pascal Retailleau 1 , Alain Brunelle 1 , Pieter C. Dorrestein 3, 4 , Jean Costa 2 , Luis M. Bedoya 6, 7 , Fanny Roussi 1 , Pieter Leyssen 8 , José Alcami 6, 7 , Julien Paolini 2 , Marc Litaudon 1 , David Touboul 1
Affiliation
A supercritical fluid chromatography-based targeted purification procedure using tandem mass spectrometry and molecular networking was developed to analyze, annotate, and isolate secondary metabolites from complex plant extract mixture. This approach was applied for the targeted isolation of new antiviral diterpene esters from Euphorbia semiperfoliata whole plant extract. The analysis of bioactive fractions revealed that unknown diterpene esters, including jatrophane esters and phorbol esters, were present in the samples. The purification procedure using semipreparative supercritical fluid chromatography led to the isolation and identification of two new jatrophane esters (13 and 14) and one known (15) and three new 4-deoxyphorbol esters (16–18). The structure and absolute configuration of compound 16 were confirmed by X-ray crystallography. This compound was found to display antiviral activity against Chikungunya virus (EC50 = 0.45 μM), while compound 15 proved to be a potent and selective inhibitor of HIV-1 replication in a recombinant virus assay (EC50 = 13 nM). This study showed that a supercritical fluid chromatography-based protocol and molecular networking can facilitate and accelerate the discovery of bioactive small molecules by targeting molecules of interest, while minimizing the use of toxic solvents.
中文翻译:
基于超临界流体色谱和串联质谱分子网络的环境友好型程序,用于从半夏大戟中发现有效的抗病毒化合物
基于串联色谱和分子网络的基于超临界流体色谱的目标纯化程序已开发出来,用于分析,注释和分离复杂植物提取物混合物中的次生代谢产物。该方法用于从大戟全植物提取物中有针对性地分离新的抗病毒二萜酯。对生物活性成分的分析表明,样品中存在未知的二萜酯,包括麻疯树酯和佛波醇酯。使用半制备超临界流体色谱进行纯化的过程导致分离和鉴定了两种新的麻疯树酯(13和14)和一种已知的(15))和三个新的4 deoxyphorbol酯(16 - 18)。通过X射线晶体学确认化合物16的结构和绝对构型。发现该化合物显示出对基孔肯雅病毒的抗病毒活性(EC 50 = 0.45μM),而在重组病毒测定中,该化合物15被证明是HIV-1复制的有效和选择性抑制剂(EC 50 = 13 nM)。这项研究表明,基于超临界流体色谱的方案和分子网络可以通过靶向目标分子来促进并加速生物活性小分子的发现,同时最大程度地减少有毒溶剂的使用。
更新日期:2017-09-19
中文翻译:
基于超临界流体色谱和串联质谱分子网络的环境友好型程序,用于从半夏大戟中发现有效的抗病毒化合物
基于串联色谱和分子网络的基于超临界流体色谱的目标纯化程序已开发出来,用于分析,注释和分离复杂植物提取物混合物中的次生代谢产物。该方法用于从大戟全植物提取物中有针对性地分离新的抗病毒二萜酯。对生物活性成分的分析表明,样品中存在未知的二萜酯,包括麻疯树酯和佛波醇酯。使用半制备超临界流体色谱进行纯化的过程导致分离和鉴定了两种新的麻疯树酯(13和14)和一种已知的(15))和三个新的4 deoxyphorbol酯(16 - 18)。通过X射线晶体学确认化合物16的结构和绝对构型。发现该化合物显示出对基孔肯雅病毒的抗病毒活性(EC 50 = 0.45μM),而在重组病毒测定中,该化合物15被证明是HIV-1复制的有效和选择性抑制剂(EC 50 = 13 nM)。这项研究表明,基于超临界流体色谱的方案和分子网络可以通过靶向目标分子来促进并加速生物活性小分子的发现,同时最大程度地减少有毒溶剂的使用。