Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B
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...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/11/459 |
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| author | Noemi Tocci Tobias Weil Daniele Perenzoni Marco Moretto Nicolai Nürk Santiago Madriñán Ruggero Ferrazza Graziano Guella Fulvio Mattivi |
| author_facet | Noemi Tocci Tobias Weil Daniele Perenzoni Marco Moretto Nicolai Nürk Santiago Madriñán Ruggero Ferrazza Graziano Guella Fulvio Mattivi |
| author_sort | Noemi Tocci |
| collection | DOAJ |
| description | 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 <i>Hypericum mexicanum</i>. 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-<i>Candida</i> 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. |
| first_indexed | 2024-03-10T14:52:40Z |
| format | Article |
| id | doaj.art-376e59561eae4692a1e6807c8536e9ff |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T14:52:40Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-376e59561eae4692a1e6807c8536e9ff2023-11-20T20:50:43ZengMDPI AGMetabolites2218-19892020-11-01101145910.3390/metabo10110459Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin BNoemi Tocci0Tobias Weil1Daniele Perenzoni2Marco Moretto3Nicolai Nürk4Santiago Madriñán5Ruggero Ferrazza6Graziano Guella7Fulvio Mattivi8Research and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all’Adige (TN), ItalyResearch and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all’Adige (TN), ItalyResearch and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all’Adige (TN), ItalyResearch and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all’Adige (TN), ItalyDepartment of Plant Systematics, BayCEER, University of Bayreuth, 95447 Bayreuth, GermanyDepartamento de Ciencias Biológicas, Universidad de los Andes, Bogotá 111711, ColombiaDepartment of Physics, University of Trento, 38123 Trento, ItalyDepartment of Physics, University of Trento, 38123 Trento, ItalyResearch and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all’Adige (TN), ItalyThe 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 <i>Hypericum mexicanum</i>. 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-<i>Candida</i> 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.https://www.mdpi.com/2218-1989/10/11/459<i>Hypericum</i>bioactive compoundsantifungal activityacylphloroglucinolsstructural annotationnuclear magnetic resonance spectroscopy |
| spellingShingle | Noemi Tocci Tobias Weil Daniele Perenzoni Marco Moretto Nicolai Nürk Santiago Madriñán Ruggero Ferrazza Graziano Guella Fulvio Mattivi Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B Metabolites <i>Hypericum</i> bioactive compounds antifungal activity acylphloroglucinols structural annotation nuclear magnetic resonance spectroscopy |
| title | Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B |
| title_full | Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B |
| title_fullStr | Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B |
| title_full_unstemmed | Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B |
| title_short | Potent Antifungal Properties of Dimeric Acylphloroglucinols from <i>Hypericum mexicanum</i> and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B |
| title_sort | potent antifungal properties of dimeric acylphloroglucinols from i hypericum mexicanum i and mechanism of action of a highly active 3 prenyl uliginosin b |
| topic | <i>Hypericum</i> bioactive compounds antifungal activity acylphloroglucinols structural annotation nuclear magnetic resonance spectroscopy |
| url | https://www.mdpi.com/2218-1989/10/11/459 |
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