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化学计量学评价杜松属和鬼臼属中抗癌前体药物鬼臼毒素及其潜在治疗类似物。

Chemometric evaluation of the anti-cancer pro-drug podophyllotoxin and potential therapeutic analogues in Juniperus and Podophyllum species.

机构信息

Institut für Umweltforschung (INFU), Technische Universität Dortmund, Otto-Hahn-Strasse 6, D-44221 Dortmund, Germany.

出版信息

Phytochem Anal. 2011 Mar-Apr;22(2):128-43. doi: 10.1002/pca.1258. Epub 2010 Nov 2.

DOI:10.1002/pca.1258
PMID:21046682
Abstract

INTRODUCTION

Podophyllotoxin, deoxypodophyllotoxin, demethylpodophyllotoxin and podophyllotoxone are four therapeutically potent secondary metabolites. There is a dearth of information on the holistic analysis of their distribution pattern in both phylogenetic and ecological contexts.

OBJECTIVES

To analyse the continuum of the above metabolites in Juniperus and Podophyllum species collected from natural populations in Himalayan environments and the botanical gardens of Rombergpark and Haltern (Germany) using multi-component LC-ESI-MS/MS, coupled with statistically relevant chemometric assessment.

METHODOLOGY

We evaluated the individual and holistic metabolite profiles and chemometrically correlated the phytochemical loads between various species (infraspecific), organic and aqueous extracts, and populations of the same species from different locations, different species from same location, different species from different locations and infrageneric populations from same and different locations.

RESULTS

Multivariate analysis revealed Juniperus x-media Pfitzeriana as a suitable alternative to Podophyllum hexandrum for commercial exploitation. A significant positive correlation of podophyllotoxone with both podophyllotoxin and demethylpodophyllotoxin, and a negative correlation of podophyllotoxin with both deoxypodophyllotoxin and demethylpodophyllotoxin (infraspecific among Podophyllum), were observed by Kruskal's multidimensional scaling and corroborated by principal component analysis, indicating probable similarity and/or difference between the biosynthetic pathways, and synergistic and/or antagonistic principles, respectively. Finally, linear discriminant analysis and hierarchical agglomerative cluster analysis revealed considerable infrageneric and infraspecific variability in secondary compound spectra and load of the different populations under study.

CONCLUSION

Such holistic studies of plants and their therapeutic metabolites ought to assist in selecting plants, geographical areas and environmental conditions for bioprospecting and global-scale phytochemical and phylogenetic diversity studies in the future.

摘要

简介

鬼臼毒素、脱氧鬼臼毒素、去甲鬼臼毒素和鬼臼毒素酮是四种具有治疗潜力的次生代谢物。关于它们在系统发育和生态背景下的分布模式的整体分析信息很少。

目的

使用多组分 LC-ESI-MS/MS 结合具有统计学意义的化学计量评估,分析从喜马拉雅环境中的自然种群以及 Rombergpark 和 Haltern(德国)植物园中收集的 Juniperus 和 Podophyllum 物种中上述代谢物的连续体。

方法

我们评估了个体和整体代谢物谱,并对不同物种(种下)、有机和水提物之间的植物化学负荷进行了化学计量相关性分析,以及来自不同地点的同一物种、来自同一地点的不同物种、来自不同地点的不同物种和来自同一和不同地点的种下种群。

结果

多元分析显示 Juniperus x-media Pfitzeriana 是替代 Podophyllum hexandrum 进行商业开发的合适替代品。鬼臼毒素酮与鬼臼毒素和去甲鬼臼毒素呈显著正相关,而鬼臼毒素与脱氧鬼臼毒素和去甲鬼臼毒素呈显著负相关(Podophyllum 种下),通过克鲁斯卡尔多维尺度分析和主成分分析得到证实,表明生物合成途径之间可能存在相似性和/或差异,以及协同和/或拮抗原则。最后,线性判别分析和层次聚类分析揭示了研究中不同种群的次级化合物谱和负荷具有相当大的种下和种下变异性。

结论

对植物及其治疗代谢物进行这种整体研究应该有助于选择植物、地理区域和环境条件,以便将来进行生物勘探和全球范围内的植物化学和系统发育多样性研究。

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