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DOI: 10.1055/s-0034-1394491
Dereplication and metabolomics strategies for the discovery of bioactive natural products: The Acronychia example
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