Targeted Isolation of Indolopyridoquinazoline Alkaloids from Conchocarpus fontanesianus Based on Molecular Networks

Article Article scientifique Article Targeted Isolation of Indolopyridoquinazoline Alkaloids from Conchocarpus fontanesianus Based on Molecular Networks eng 2016 author Cabral-Cabeca Rodrigo 812154 author Allard Pierre-Marie 812151 author Marcourt Laurence 729234 author Young Maria Cláudia Marx author Ferreira Queiroz Emerson 135675 author Wolfender Jean-Luc 135649 2270-2278 10.1021/acs.jnatprod.6b00379 27557347 0163-3864 A dichloromethane-soluble fraction of the stem bark of Conchocarpus fontanesianus showed antifungal activity against Candida albicans in a bioautography assay. Off-line high-pressure liquid chromatography activity-based profiling of this extract enabled a precise localization of the compounds responsible for the antifungal activity that were isolated and identified as the known compounds flindersine (17) and 8-methoxyflindersine (18). As well as the identification of the bioactive principles, the ultra-high-pressure liquid chromatography-high-resolution mass spectrometry metabolite profiling of the dichloromethane stem bark fraction allowed the detection of more than 1000 components. Some of these could be assigned putatively to secondary metabolites previously isolated from the family Rutaceae. Generation of a molecular network based on MS(2) spectra indicated the presence of indolopyridoquinazoline alkaloids and related scaffolds. Efficient targeted isolation of these compounds was performed by geometric transfer of the analytical high-pressure liquid chromatography profiling conditions to preparative medium-pressure liquid chromatography. This yielded six new indolopyridoquinazoline alkaloids (5, 16, 19-22) that were assigned structurally. The medium-pressure liquid chromatography separations afforded additionally 16 other compounds. This work has demonstrated the usefulness of molecular networks to target the isolation of new natural products and the value of this approach for dereplication. A detailed analysis of the constituents of the stem bark of C. fontanesianus was conducted. Alkaloids/chemistry/isolation & purification/pharmacology Antifungal Agents/chemistry/isolation & purification/pharmacology Biological Products/chemistry/isolation & purification/pharmacology Brazil Candida albicans/drug effects Chromatography, High Pressure Liquid Nuclear Magnetic Resonance, Biomolecular Plant Bark/chemistry Rutaceae/chemistry Dewey 615 31 Section des sciences pharmaceutiques 17 false 882 Phytochimie et produits naturels bioactifs Journal of Natural Products 79 9 f3ff7039-a79e-4e82-bb30-49ca9428ebd3 Article (Published version) Restricted Cabral-2016-Targeted.pdf 384799 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Targeted Isolation of Indolopyridoquinazoline Alkaloids from Conchocarpus fontanesianus Based on Molecular Networks	Journal of Natural Products			2016	274	0

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