Opportunities and Limitations for Untargeted Mass Spectrometry Metabolomics to Identify Biologically Active Constituents in Complex Natural Product Mixtures.
J Nat Prod
; 82(3): 469-484, 2019 03 22.
Article
em En
| MEDLINE
| ID: mdl-30844279
ABSTRACT
Compounds derived from natural sources represent the majority of small-molecule drugs utilized today. Plants, owing to their complex biosynthetic pathways, are poised to synthesize diverse secondary metabolites that selectively target biological macromolecules. Despite the vast chemical landscape of botanicals, drug discovery programs from these sources have diminished due to the costly and time-consuming nature of standard practices and high rates of compound rediscovery. Untargeted metabolomics approaches that integrate biological and chemical data sets potentially enable the prediction of active constituents early in the fractionation process. However, data acquisition and data processing parameters may have major impacts on the success of models produced. Using an inactive botanical mixture spiked with known antimicrobial compounds, untargeted mass spectrometry-based metabolomics data were combined with bioactivity data to produce selectivity ratio models subjected to a variety of data acquisition and data processing parameters. Selectivity ratio models were used to identify active constituents that were intentionally added to the mixture, along with an additional antimicrobial compound, randainal (5), which was masked by the presence of antagonists in the mixture. These studies found that data-processing approaches, particularly data transformation and model simplification tools using a variance cutoff, had significant impacts on the models produced, either masking or enhancing the ability to detect active constituents in samples. The current study highlights the importance of the data processing step for obtaining reliable information from metabolomics models and demonstrates the strengths and limitations of selectivity ratio analysis to comprehensively assess complex botanical mixtures.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Espectrometria de Massas
/
Produtos Biológicos
/
Misturas Complexas
/
Metabolômica
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos