1. Anti-Candida Cassane-Type Diterpenoids from the Root Bark of Swartzia simplex.
- Author
-
Favre-Godal Q, Dorsaz S, Queiroz EF, Marcourt L, Ebrahimi SN, Allard PM, Voinesco F, Hamburger M, Gupta MP, Gindro K, Sanglard D, and Wolfender JL
- Subjects
- Antifungal Agents chemistry, Biological Products chemistry, Chromatography, High Pressure Liquid, Diterpenes chemistry, Humans, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Panama, Plant Bark chemistry, Antifungal Agents isolation & purification, Antifungal Agents pharmacology, Biological Products isolation & purification, Biological Products pharmacology, Candida albicans drug effects, Diterpenes isolation & purification, Diterpenes pharmacology, Fabaceae chemistry
- 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.
- Published
- 2015
- Full Text
- View/download PDF