Tools and strategies to prioritize the discovery of bioactive natural products – An MS and NMR based metabolomics perspective

The recent rapid innovations made in metabolite profiling and bioassays may lead to a change of paradigm in natural products research. Indeed having at hand full or partial of structure of possibly all metabolites in given natural extract at different quantitative levels open the possibility to perform pharmacognosy studies from a more holistic perspective. The increasingly amount of accurate metabolome data that can be acquired on massive sample sets, notably through high resolution mass spectrometry data dependent MS/MS analyses (HRMS/MS), allows mapping of natural extracts at an unprecedented precision level.1,2 While the acquisition of larger volumes of data is ongoing, contextualizing it is a lagging process. For this the establishment of integrated and open databases ecosystem could be extremely valuable to nurture pharmacognosy in the years to come and have finally general positive societal outomes.3 Fast progresses are foreseen bringing together recent computational / analytical approaches linking invaluable published knowledge brought by pharmacognosy mainly based on bioactivity guided isolation studies. In this context we push forward our applications and further development of UHPLC-HRMS/MS Molecular network (MN) approaches4,5 to provide enhanced annotation confidence level though multiple scores integrating notably taxonomy information and MN structural consistency as well as other orthogonal analytical data (chromatographic retention, Collisional Cross Section in IMS…). Benchmarking of such approaches is currently assessed by profiling mixtures of herbs with well-studied composition. Different recent applications of our metabolomics and phytochemical investigations will illustrated these aspects. An ideal workflow will be presented and discussion on what is readily implemented and is still required will be made, notably in term of contextualisation of the data.