title: Evaluation of Jatrophane Esters from Euphorbia spp. as Modulators of Candida albicans Multidrug Transporters.
abstract: Twenty-nine jatrophane esters (1-10, 12-30) and one lathyrane (11) diterpenoid ester isolated from Euphorbia species were evaluated for their capacity to inhibit drug-efflux activities of the primary ABC transporter CaCdr1p and the secondary MFS transporter CaMdr1p of Candida albicans, in yeast strains overexpressing the corresponding transporter. These diterpenoid esters were obtained from Euphorbia semiperfoliata (1-10), E. insularis (11), and E. dendroides (12-30) and included five new compounds, euphodendroidins P-T (26-30). The jatrophane esters 12 and 23 were found to inhibit the efflux of Nile Red (NR) mediated by the two multidrug transporters, at 85-64% for CaCdr1p and 79-65% for CaMdr1p. In contrast, compound 21 was selective for CaCdr1p and induced a strong inhibition (92%), whereas compound 8 was selective for CaMdr1p, with a 74% inhibition. It was demonstrated further that potency and selectivity are sensitive to the substitution pattern on the jatrophane skeleton. However, these compounds were not transported and showed no synergism with fluconazole cytotoxicity.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, ICSN UPR 2301, University of Paris-Saclay , 91198, Gif-sur-Yvette, France.|Laboratoire de Chimie des Produits Naturels, CNRS, UMR SPE 6134, University of Corsica , 20250, Corte, France.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Esposito
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University , 110067, New Delhi, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Nim
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, ICSN UPR 2301, University of Paris-Saclay , 91198, Gif-sur-Yvette, France.|Laboratoire de Chimie des Produits Naturels, CNRS, UMR SPE 6134, University of Corsica , 20250, Corte, France.
authors.forename: Louis-Félix
authors.initials: LF
authors.lastname: Nothias
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, ICSN UPR 2301, University of Paris-Saclay , 91198, Gif-sur-Yvette, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gallard
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, ICSN UPR 2301, University of Paris-Saclay , 91198, Gif-sur-Yvette, France.|School of Life Sciences, Jawaharlal Nehru University , 110067, New Delhi, India.
authors.forename: Manpreet Kaur
authors.initials: MK
authors.lastname: Rawal
authors.affiliation: Laboratoire de Chimie des Produits Naturels, CNRS, UMR SPE 6134, University of Corsica , 20250, Corte, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Costa
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, ICSN UPR 2301, University of Paris-Saclay , 91198, Gif-sur-Yvette, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Roussi
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University , 110067, New Delhi, India.
authors.forename: Rajendra
authors.identifier: 0000-0002-8044-7042
authors.initials: R
authors.lastname: Prasad
authors.affiliation: MMSB, UMR 5086 CNRS-University of Lyon, Institute of Protein Biology and Chemistry , 69367, Lyon, France.
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Pietro
authors.affiliation: Laboratoire de Chimie des Produits Naturels, CNRS, UMR SPE 6134, University of Corsica , 20250, Corte, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Paolini
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, ICSN UPR 2301, University of Paris-Saclay , 91198, Gif-sur-Yvette, France.
authors.forename: Marc
authors.identifier: 0000-0002-0877-8234
authors.initials: M
authors.lastname: Litaudon
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004952:Esters; D028481:Euphorbia / Q000737:chemistry*; D015725:Fluconazole / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D004224:Diterpenes; D004952:Esters; D026901:Membrane Transport Proteins; C530345:jatrophane; C530347:lathyrane; D015725:Fluconazole