Unbiased evaluation of bioactive secondary metabolites in complex matrices.
Unbiased evaluation of bioactive secondary metabolites in complex matrices.
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DOI：
10.1016/j.fitote.2012.06.012
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发表时间：
2012-10
期刊：
影响因子：
3.4
通讯作者：
Pauli, Guido F.
中科院分区：
文献类型：
--
作者：
Inui, Taichi;Wang, Yuehong;Pro, Samuel M.;Franzblau, Scott G.;Pauli, Guido F.
关键词：
复杂基质中的大多数生物活性成分，如天然产物和植物药物，都是次生代谢产物，而不是初级代谢产物。除了具有化学多样性外，民族植物的生物活性可以包括一种至几种生物活性化合物，以复杂混合物的形式存在。传统的发现工作利用生物测定引导分离（BGF）来分离单个活性化合物。当应用于复杂的天然产物时，BGF在分馏过程中经常受到活性明显丧失的挑战，导致活性较弱的分离化合物。代谢组学分析可以通过捕获代谢物的化学复杂性来潜在地补充现有的BGF范式。提出的生物化学计量学方法使用高通量、高分辨率的生物学终点，建立了二级代谢组化学与应有的健康影响之间的联系。对阿拉斯加民族植物Oplopanax horridus的抗结核（TB）活性进行了原理证明。生物化学计量学分析采用二维正交色谱逆流法和气相色谱-质谱法从活性提取物中数千种代谢物中鉴定出100种最有效成分。利用先前分离的水蛭植物成分作为已知结构和生物活性的参考标记。正相关可以区分抗结核活性和非活性化合物。MS数据鉴定出3个主要结构类共29种活性物质。生物化学计量分析是草药和民族植物药标准化的新工具，也是从自然界发现药物的新工具。该方法可以在复杂混合物中分配多个活性化合物，而无需事先分离或结构解析，同时仍然提供结构信息的接口。
The majority of bioactive principles in a complex matrix such as natural products and botanical medicines are secondary rather than primary metabolites. In addition to being chemically diverse, the bioactivity of an ethnobotanical can comprise from one to several bioactive compounds, present in a complex mixture. Conventional discovery efforts utilize bioassay-guided fractionation (BGF) to isolate individual active compounds. When applied to complex natural products, BGF is often challenged by an apparent loss of activity during fractionation, resulting in weakly active isolated compounds. Metabolomic analysis can potentially complement existing the BGF paradigm by capturing the chemical complexity of the metabolites. The proposed biochemometric approach establishes a link between the chemistry of a secondary metabolome and a deserved health impact, using a high-throughput, high-resolution capable biological endpoint. The proof of principle is demonstrated for the anti-tuberculosis (TB) activity of the Alaskan ethnobotanical, Oplopanax horridus. Biochemometric analysis identified the 100 most active constituents from thousands of metabolites in the active extract by means of 2D orthogonal chromatography using countercurrent and GC-MS methods. Previously isolated O. horridus phytoconstituents were used as reference markers of known structure and bio(in)activity. Positive correlations allowed distinction of anti-TB actives from inactive compounds. A total of 29 bioactives from 3 main structural classes were assigned based on MS data. Biochemometric analysis is a new tool for the standardization of herbal medicines and ethnobotanicals, as well as for drug discovery from nature. The method can assign multiple active compounds in complex mixtures without their prior isolation or structure elucidation, while still providing an interface to structural information.
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影响因子：
3.8
作者：
Tohge, Takayuki;Fernie, Alisdair R.
通讯作者：
Fernie, Alisdair R.
影响因子：
5.1
作者：
Kobaisy, M;Abramowski, Z;Stokes, RW
通讯作者：
Stokes, RW
影响因子：
7.2
作者：
Saludes, JP;Garson, MJ;Aguinaldo, AM
通讯作者：
Aguinaldo, AM
DOI：
10.1073/pnas.0503647102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Koch, MA;Schuffenhauer, A;Waldmann, H
通讯作者：
Waldmann, H
影响因子：
4.1
作者：
Johnson, KJ;Wright, BW;Synovec, RE
通讯作者：
Synovec, RE