High-resolution screening combined with HPLC-HRMS-SPE-NMR for identification of fungal plasma membrane H(+)-ATPase inhibitors from plants.
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.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Kenneth T
KT
Kongstad
Sileshi G
SG
Wubshet
Ane
A
Johannesen
Lasse
L
Kjellerup
Anne-Marie Lund
AM
Winther
Anna Katharina
AK
Jäger
Dan
D
Staerk
D001578:Benzopyrans / Q000032:analysis / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D005658:Fungi / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D005960:Glucosides / Q000032:analysis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D043842:Ochnaceae / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D029631:Sapindaceae / Q000737:chemistry; D052616:Solid Phase Extraction
D001578:Benzopyrans; D004791:Enzyme Inhibitors; D005960:Glucosides; D010936:Plant Extracts; C473299:tellimagrandin II; C076178:chebulagic acid; D005707:Gallic Acid; D006180:Proton-Translocating ATPases