Isolation of Picrotoxanes from Austrobuxus carunculatus Using Taxonomy-Based Molecular Networking
| Autor: | David Touboul, Pascal Retailleau, Cécile Apel, Florent Olivon, Sandy Desrat, Fanny Roussi, Marc Litaudon |
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| Přispěvatelé: | Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Metabolite Pharmaceutical Science 01 natural sciences Analytical Chemistry chemistry.chemical_compound Sensu [CHIM.ANAL]Chemical Sciences/Analytical chemistry Drug Discovery Molecule [CHIM]Chemical Sciences ComputingMilieux_MISCELLANEOUS Pharmacology biology 010405 organic chemistry Chemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry Organic Chemistry Tutin biology.organism_classification Austrobuxus 0104 chemical sciences [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry 010404 medicinal & biomolecular chemistry Complementary and alternative medicine Molecular networking Molecular Medicine Taxonomy (biology) Specific rotation [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology [SDE.BE]Environmental Sciences/Biodiversity and Ecology [CHIM.OTHE]Chemical Sciences/Other [CHIM.CHEM]Chemical Sciences/Cheminformatics |
| Zdroj: | Journal of Natural Products Journal of Natural Products, American Chemical Society, 2020, 83 (10), pp.3069-3079. ⟨10.1021/acs.jnatprod.0c00636⟩ |
| ISSN: | 0163-3864 1520-6025 |
| Popis: | A unique collection of 292 extracts from 107 New Caledonian Euphorbiaceae species sensu lato was profiled by LC-MS2 and the metabolite content organized by molecular networking. Based on the assumption that taxon-specific molecules are more likely to be structurally novel, taxonomic data were mapped on spectral networks to detect genus-specific clusters. Using this approach, a group of compounds unique to the genus Austrobuxus was highlighted. The subsequent MS-guided purification of the fruit EtOAc extract of Austrobuxus carunculatus led to the isolation of 13 new monolactone and "norditerpene" picrotoxanes (2-14), along with the known tutin (1). The structures of the new compounds were elucidated by HRESIMS and NMR spectroscopic data analysis, and the absolute configurations of compounds 1, 3, 7, 11, 12, and 14 were determined by single-crystal X-ray diffraction analysis. The relative and absolute configurations of compounds 4 and 5 were ascertained by chemical transformation of compound 3. The absolute configurations of other members of the series have been proposed on the basis of biogenetic considerations and specific rotation values of similar sign and magnitude. Compounds 1-14 were evaluated for their antiproliferative activities against HCT116 colon, U87-MG glioblastoma, and A549 lung human cancer cell lines. Compounds bearing an acyl chain at C-2 (i.e., 2, 4, and 13) showed IC50 values in the micromolar range for the three cell lines used. |
| Databáze: | OpenAIRE |
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