The success of antifungal therapies is often hindered by the limited number of available drugs. To close the gap in the antifungal pipeline, the search of novel leads is of primary importance, and here the exploration of neglected plants has great promise for the discovery of new principles. Through bioassay-guided isolation, uliginosin B and five new dimeric acylphloroglucinols (uliginosins C-D, and 3′prenyl uliginosins B-D), besides cembrenoids, have been isolated from the lipophilic extract of Hypericum mexicanum. Their structures were elucidated by a combination of Liquid Chromatography - Mass Spectrometry LC-MS and Nuclear Magnetic Resonance (NMR) measurements. The compounds showed strong anti-Candida activity, also against fluconazole-resistant strains, with fungal growth inhibition properties at concentrations ranging from 3 to 32 µM, and reduced or absent cytotoxicity against human cell lines. A chemogenomic screen of 3′prenyl uliginosin B revealed target genes that are important for cell cycle regulation and cytoskeleton assembly in fungi. Taken together, our study suggests dimeric acylphloroglucinols as potential candidates for the development of alternative antifungal therapies

Tocci, N.; Weil, T.; Perenzoni, D.; Moretto, M.; Nürk, N.; Madriñán, S.; Ferrazza, R.; Guella, G.; Mattivi, F. (2020). Potent antifungal properties of dimeric acylphloroglucinols from hypericum mexicanum and mechanism of action of a highly active 3′prenyl uliginosin B. METABOLITES, 10 (11): 459. doi: 10.3390/metabo10110459 handle: http://hdl.handle.net/10449/65448

Potent antifungal properties of dimeric acylphloroglucinols from hypericum mexicanum and mechanism of action of a highly active 3′prenyl uliginosin B

Tocci, N.
Primo
;
Weil, T.;Perenzoni, D.;Moretto, M.;Mattivi, F.
Ultimo
2020-01-01

Abstract

The success of antifungal therapies is often hindered by the limited number of available drugs. To close the gap in the antifungal pipeline, the search of novel leads is of primary importance, and here the exploration of neglected plants has great promise for the discovery of new principles. Through bioassay-guided isolation, uliginosin B and five new dimeric acylphloroglucinols (uliginosins C-D, and 3′prenyl uliginosins B-D), besides cembrenoids, have been isolated from the lipophilic extract of Hypericum mexicanum. Their structures were elucidated by a combination of Liquid Chromatography - Mass Spectrometry LC-MS and Nuclear Magnetic Resonance (NMR) measurements. The compounds showed strong anti-Candida activity, also against fluconazole-resistant strains, with fungal growth inhibition properties at concentrations ranging from 3 to 32 µM, and reduced or absent cytotoxicity against human cell lines. A chemogenomic screen of 3′prenyl uliginosin B revealed target genes that are important for cell cycle regulation and cytoskeleton assembly in fungi. Taken together, our study suggests dimeric acylphloroglucinols as potential candidates for the development of alternative antifungal therapies
Hypericum
Bioactive compounds
Antifungal activity
Acylphloroglucinols
Structural annotation
Nuclear magnetic resonance spectroscopy
Mass spectrometry
Cytotoxicity
Mechanism of action
Settore BIO/15 - BIOLOGIA FARMACEUTICA
2020
Tocci, N.; Weil, T.; Perenzoni, D.; Moretto, M.; Nürk, N.; Madriñán, S.; Ferrazza, R.; Guella, G.; Mattivi, F. (2020). Potent antifungal properties of dimeric acylphloroglucinols from hypericum mexicanum and mechanism of action of a highly active 3′prenyl uliginosin B. METABOLITES, 10 (11): 459. doi: 10.3390/metabo10110459 handle: http://hdl.handle.net/10449/65448
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