Metabolomics for bioactivity assessment of natural products

Abstract

Natural products historically have been a rich source of lead molecules in drug discovery, based on their capability to create unique and diverse chemical structures. However, it is also true that the vast number of metabolites typically present in natural products and their huge dynamic range results in the loss of many possibly bioactive natural compounds, becoming an inextricable obstacle for drug development. Recently, new strategies which favour a holistic approach as opposed to the traditional reductionist methods used previously, have been introduced with the purpose of overcoming the bottlenecks in natural product research. This approach is based on the application of new technologies, including metabolomics, for example. Metabolomics allows a systematic study of a complex mixture such as a phytochemical preparation, which can be linked to observations obtained through biological testing systems without the need for isolating active principles. This may put drug discovery from natural products back in the limelight again. In this review paper, the description of some examples of successful metabolomics applications in several important fields related to drug discovery from natural sources aims at raising the potential of metabolomics in reducing the gap between natural products (NP) and modern drug discovery demand. Copyright © 2010 John Wiley & Sons, Ltd.

Differentiation of five pine species cultivated in Brazil based on chemometric analysis of their volatiles identified by gas chromatography-mass spectrometry

“…The strong influence of (+)-α-pinene for P. taeda and (-)-β-pinene for P. elliottii was observed by Gomes da Silva et al 17 in extracts from needles of Pinus from central Portugal. (12) and thymol methyl ether (14), and the larger amount of β-phellandrene (10). Meanwhile, (-)-α-pinene (2), (+)-β-pinene (5), δ-2-carene (8) and terpinolene (11) allowed the differentiation of P. maximinoi samples.…”

“…The volatiles p-mentha-2,4(8)-diene (12) and thymol methyl ether (14) were found only in P. patula samples, while methyl octanoate (13) was found only in P. taeda samples (Table 2). If these compounds are in fact being produced only by these respective species, they could be used as chemical markers; however, the design of the present study does not permit this conclusion.…”

“…6 Chemometric and bioinformatic methodologies are being extensively applied in taxonomic and metabolomic studies. [7][8][9][10][11][12][13][14] For instance, Scrivant et al 15 succeeded in delimiting the species of Bothriochloa, by studying the essential oil composition by means of GC-MS (gas chromatography-mass spectrometry). Fischedick et al 16 discriminated varieties of Cannabis by GC, using the quantitative data for monoterpenoids, sesquiterpenoids and cannabinoids.…”

The emergence of metabolomics as a key discipline in the drug discovery process

“…More particularly in the pharmaceutical field, metabolomic techniques and applications find scope from drug discovery to clinical development of new medicines. This includes target identification and validation, elucidation of the mechanisms of action of drugs, lead identification [9,10], identification of drug efficacy or pathology biomarkers [11][12][13], toxicological analysis by identification of safety biomarkers [14][15][16] but also quality control, particularly of medicinal plants [17,18] and bioactive drug discovery from natural sources [19] .…”

Identifying biochemical phenotypic differences between cryptic species

“…Untargeted metabolic profiling (metabolomics) offers one of the most direct measures of cellular phenotype: it integrates the effects of regulation at different biological levelstranscriptional, translational and post-translational [3]. Metabolomics has been frequently used as a chemotaxonomic tool for classifying different groups, most usually of plants, but previous studies have generally focused on well-defined populations or cultivars; often, samples from different geographical locations are analysed, with no attempt to distinguish between genetic and environmental effects [4,5]. There have been few attempts to analyse the effects of genetic variation on metabolome profiles in an environmental context [5][6][7].…”