title: Anti-Candida Cassane-Type Diterpenoids from the Root Bark of Swartzia simplex.
abstract: A dichloromethane extract of the roots from the Panamanian plant Swartzia simplex exhibited a strong antifungal activity in a bioautography assay against a genetically modified hypersusceptible strain of Candida albicans. At-line HPLC activity based profiling of the crude extract enabled a precise localization of the antifungal compounds, and dereplication by UHPLC-HRESIMS indicated the presence of potentially new metabolites. Transposition of the HPLC reversed-phase analytical conditions to medium-pressure liquid chromatography (MPLC) allowed an efficient isolation of the major constituents. Minor compounds of interest were isolated from the MPLC fractions using semipreparative HPLC. Using this strategy, 14 diterpenes (1-14) were isolated, with seven (5-10, 14) being new antifungal natural products. The new structures were elucidated using NMR spectroscopy and HRESIMS analysis. The absolute configurations of some of the compounds were elucidated by electronic circular dichroism spectroscopy. The antifungal properties of these compounds were evaluated as their minimum inhibitory concentrations in a dilution assay against both hypersusceptible and wild-type strains of C. albicans and by assessment of their antibiofilm activities. The potential cytological effects on the ultrastructure of C. albicans of the antifungal compounds isolated were evaluated on thin sections by transmission electron microscopy.
authors.affiliation: School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne , 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Favre-Godal
authors.affiliation: Institute of Microbiology, University of Lausanne and University Hospital Center , Rue du Bugnon 48, CH-1011 Lausanne, Switzerland.
authors.forename: Stephane
authors.initials: S
authors.lastname: Dorsaz
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 F
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: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , G. C., Evin, P.O. Box 19835-389, Tehran, Iran.
authors.forename: Samad N
authors.initials: SN
authors.lastname: Ebrahimi
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: Agroscope, Institute for Plant Production Sciences (IPS), Mycology and Biotechnology , Route de Duiller 50, P.O. Box 1012, CH-1260 Nyon, Switzerland.
authors.forename: Francine
authors.initials: F
authors.lastname: Voinesco
authors.affiliation: Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel , Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
authors.affiliation: Center for Pharmacognostic Research on Panamanian Flora (CIFLORPAN), University of Panama , P.O. Box 0824-00172, Panama City, Panama.
authors.forename: Mahabir P
authors.initials: MP
authors.lastname: Gupta
authors.affiliation: Agroscope, Institute for Plant Production Sciences (IPS), Mycology and Biotechnology , Route de Duiller 50, P.O. Box 1012, CH-1260 Nyon, Switzerland.
authors.forename: Katia
authors.initials: K
authors.lastname: Gindro
authors.affiliation: Institute of Microbiology, University of Lausanne and University Hospital Center , Rue du Bugnon 48, CH-1011 Lausanne, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
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: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007887:Fabaceae / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010176:Panama; D024301:Plant Bark / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D004224:Diterpenes