Planta Med 2014; 80 - SL3
DOI: 10.1055/s-0034-1394491

Dereplication and metabolomics strategies for the discovery of bioactive natural products: The Acronychia example

E Kouloura 1, 2, G Genta-Jouve 2, C Pergola 3, V Krauth 3, M Litaudon 4, D Benaki 5, O Wertz 3, S Michel 2, E Mikros 5, L Skaltsounis 1, M Halabalaki 1
  • 1Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, University of Athens, Athens 15771, Greece
  • 2Laboratoire de Pharmacognosie de l'Université Paris Descartes, UMR/CNRS 8638 COMETE, Faculté de Pharmacie, 4 Avenue de l'Observatoire, F-75006 Paris, France
  • 3Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University of Jena, Jena, Germany
  • 4Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 1, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
  • 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens 15771, Greece

Natural products (NPs) still represent are largely untapped source for promising drug leads, and of new chemical scaffolds serving as probes or inspiration for medicinal chemistry. However, certain bottlenecks in the NPs discovery process hamper their exploitation and have led to a degreased interest from the major pharmaceutical companies. In recent years new tools and integrated concepts have been introduced in NPs drug discovery, thereby facilitating the discovery process. In this contribution, the study of Acronychia species (Rutaceae) is given combining both traditional and new approaches for the identification of novel active molecules. Profiling of extracts using different analytical platforms, such as LC-HRMS and MSn identification and dereplication strategies, as well as LC-HRMS and NMR-based metabolic profiling have been employed. Acronychia-type acetophenones (AtA) were isolated, structurally elucidated, and biologically evaluated for their cytotoxic and anti-inflammatory properties [1]. A fast, accurate and sensitive LC-HRMSn methodology was developed for AtA identification, and more than 25 new AtAs were discovered while an AtA specific database was established. Identification of biomarkers, data and profile-activity correlations were carried out. Finally, the metabolic profiling approaches enabled the exploration of different species, plant parts and origins, and revealed both sample-specific marker compounds and common metabolites.

Keywords: Acronychia, dereplication, metabolomics, LC-MS profiling, NMR profiling, 5-LO

References:

[1] Kouloura E, Halabalaki M, Lallemand MC, Nam S, Jove R, Litaudon M, Awang K, Hadi HA, Skaltsounis AL. Cytotoxic prenylated acetophenone dimers from Acronychia pedunculata. J Nat Prod 2012; 75:1270 – 6