The efficient identification of bioactive compounds in complex matrices, and the global chemical characterization of extracts remain major challenges in natural products research. Over the past decade, new technologies and tools have become available in the biosciences and in analytical chemistry which enable new approaches in the activity-driven search for natural products. These new possibilities can be summarized with a few keywords such as: miniaturization, on-line analysis of complex samples, chemometric data analysis, study of molecular modes of action, and systems oriented approaches towards the characterization of drug effects in vitro and in vivo.We have been exploring some of these in our lab over the past years. As a consequence, we implemented a number of technologies and approaches, such as comprehensive phytochemical profiling, NMR-based metabolomics, and a technology platform for miniaturized natural products-based lead discovery. This platform includes 2D-barcoded liquid extract libraries, HPLC-based micro-fractionation for off-line bioactivity assessment, simultaneous on-line spectroscopy (PDA, TOFMS, and MS/MS), and off-line NMR spectroscopy with a 1mm microprobe. The platform is generically applicable with mechanism-based and functional assays in the 96-well MTP format and serves as a turntable for collaborative projects in various therapeutic areas.Use of the technology platform and of different profiling approaches will be illustrated with selected examples. A case study of comprehensive phytochemical profiling and metabolomics will be presented with in vivo anti-inflammatory extracts from Isatis tinctoria. The efficient discovery of new GABAA receptor modulators, antiretroviral compounds, and kinase inhibitors of plant origin will exemplify our HPLC-based activity profiling approach for lead discovery.

Profiling approaches in natural product research

246th National Meeting (2013)

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