title: Fungal plasma membrane H⁺-ATPase inhibitory activity of o-hydroxybenzylated flavanones and chalcones from Uvaria chamae P. Beauv.
abstract: In our ongoing efforts of finding natural fungicides to fight food and feed spoilage during production and storage, the antifungal potential of Ghanaian Uvaria chamae P. Beauv. was investigated, with emphasis on plant metabolites targeting the fungal plasma membrane (PM) H(+)-ATPase. Ethyl acetate extract of U. chamae was subjected to high-resolution fungal PM H(+)-ATPase inhibition screening followed by structural elucidation by high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-HRMS-SPE-NMR). This led to identification of a series of uncommon o-hydroxybenzylated flavanones and chalcones, i.e., chamanetin (8), isochamanetin (9), isouvaretin (10), uvaretin (11), dichamanetin (12), and diuvaretin (15). Preparative-scale isolation of the active metabolites allowed determination of IC50 values for inhibition of the PM H(+)-ATPase, and growth inhibition of Saccharomyces cerevisiae and Candida albicans. These revealed a strong correlation between o-hydroxybenzyl substituents and PM H(+)-ATPase activity, with dichamanetin being the most potent compound, but showing moderate activity in the fungal growth inhibition assays.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: kenneth.kongstad@sund.ku.dk.
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Kongstad
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Sileshi G
authors.initials: SG
authors.lastname: Wubshet
authors.affiliation: PCOVERY, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Kjellerup
authors.affiliation: PCOVERY, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Anne-Marie Lund
authors.initials: AM
authors.lastname: Winther
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Dan
authors.initials: D
authors.lastname: Staerk
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D047188:Chalcones / Q000737:chemistry*; D044950:Flavanones / Q000737:chemistry*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D031046:Uvaria / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D047188:Chalcones; D044950:Flavanones; D005656:Fungal Proteins; D006180:Proton-Translocating ATPases
keywords: Chamanetin (PubChem CID: 5315801); Dichamanetin (PubChem CID: 181193); Diuvaretin (PubChem CID: 3085222); Fungal plasma membrane H(+)-ATPase; HPLC–HRMS–SPE–NMR; High-resolution screening; Isochamanetin (PubChem CID: 21721817); Pinocembrin (PubChem CID: 68071); Uvaretin (PubChem CID: 73447); Uvaria chamae