High-resolution screening combined with HPLC–HRMS–SPE–NMR for identification of fungal plasma membrane H⁺-ATPase inhibitors from plants

TY - JOUR

T1 - High-resolution screening combined with HPLC–HRMS–SPE–NMR for identification of fungal plasma membrane H+-ATPase inhibitors from plants

AU - Kongstad, Kenneth

AU - Wubshet, Sileshi Gizachew

AU - Johannesen, Ane

AU - Kjellerup, Lasse

AU - winther, Anne-Marie Lund

AU - Jäger, Anna

AU - Stærk, Dan

PY - 2014/6/18

Y1 - 2014/6/18

N2 - 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.

AB - 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.

U2 - 10.1021/jf501605z

DO - 10.1021/jf501605z

M3 - Journal article

C2 - 24830509

SN - 0021-8561

VL - 62

SP - 5595

EP - 5602

JO - Journal of Agricultural and Food Chemistry

JF - Journal of Agricultural and Food Chemistry

IS - 24

ER -