1. High-resolution screening combined with HPLC-HRMS-SPE-NMR for identification of fungal plasma membrane H(+)-ATPase inhibitors from plants.
- Author
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Kongstad KT, Wubshet SG, Johannesen A, Kjellerup L, Winther AM, Jäger AK, and Staerk D
- Subjects
- Benzopyrans analysis, Benzopyrans pharmacology, Candida albicans drug effects, Candida albicans growth & development, Enzyme Inhibitors pharmacology, Fungi metabolism, Gallic Acid analogs & derivatives, Gallic Acid analysis, Gallic Acid pharmacology, Glucosides analysis, Glucosides pharmacology, Ochnaceae chemistry, Proton-Translocating ATPases metabolism, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae growth & development, Sapindaceae chemistry, Solid Phase Extraction, Chromatography, High Pressure Liquid, Enzyme Inhibitors analysis, Magnetic Resonance Spectroscopy, Plant Extracts chemistry, Proton-Translocating ATPases antagonists & inhibitors
- Abstract
Crude extracts of 33 plant species were assessed for fungal plasma membrane (PM) H(+)-ATPase inhibition. This led to identification of 18 extracts showing more than 95% inhibition at a concentration of 7.5 mg/mL and/or a concentration-dependent activity profile. These extracts were selected for semi-high-resolution fungal PM H(+)-ATPase inhibition screening, and, on the basis of these results, Haplocoelum foliolosum (Hiern) Bullock and Sauvagesia erecta L. were selected for investigation by high-resolution fungal PM H(+)-ATPase inhibition screening. Structural analysis performed by high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-HRMS-SPE-NMR) led to identification of chebulagic acid (1) and tellimagrandin II (2) from H. foliolosum. Preparative-scale isolation of the two metabolites allowed determination of IC50 values for PM H(+)-ATPase, and growth inhibition of Saccharomyces cerevisiae and Candida albicans. Chebulagic acid and tellimagrandin II are both potent inhibitors of the PM H(+)-ATPase with inhibitory effect on the growth of S. cerevisiae.
- Published
- 2014
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