title: Targeted Isolation of Indolopyridoquinazoline Alkaloids from Conchocarpus fontanesianus Based on Molecular Networks.
abstract: 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.
authors.affiliation: Nucleus of Research in Physiology and Biochemistry, Botany Institute of São Paulo , Avenida Miguel Estefano, 3687, 04301-012, São Paulo, Brazil.|School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne , 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Rodrigo Sant'Ana
authors.initials: RS
authors.lastname: Cabral
authors.affiliation: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne , 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Allard
authors.affiliation: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne , 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.affiliation: Nucleus of Research in Physiology and Biochemistry, Botany Institute of São Paulo , Avenida Miguel Estefano, 3687, 04301-012, São Paulo, Brazil.
authors.forename: Maria Cláudia Marx
authors.initials: MC
authors.lastname: Young
authors.affiliation: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne , 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Emerson Ferreira
authors.initials: EF
authors.lastname: Queiroz
authors.affiliation: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne , 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Wolfender
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001938:Brazil; D002176:Candida albicans / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D019906:Nuclear Magnetic Resonance, Biomolecular; D024301:Plant Bark / Q000737:chemistry; D027821:Rutaceae / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000935:Antifungal Agents; D001688:Biological Products