title: Glycosidase inhibitors from the roots of Glyphaea brevis.
abstract: Ten phenylalkyl-substituted iminosugars (1-10) and a cinnamic acid derived glucoside (11) were isolated from the roots of Glyphaea brevis (Malvaceae). Their structures were elucidated by 1D and 2D NMR analysis, as well as by HR-ESIMS. Compounds 1-10 retain an unprecedented structure composed of an iminosugar-like core identified as 1-deoxyfuconojirimycin in glyphaeaside A1-A4 (1, 2, 5, 6), 1-deoxygalactonojirimycin in glyphaeaside B1-B5 (3, 4, 7-9) or 1-deoxynojirimycin in glyphaeaside C (10), substituted by a β-d-glucopyranose in compounds 2, 4, 6 and 9. These compounds feature a di-, tri- or tetra-hydroxylated nine-carbon chain at the pseudo-anomeric position, substituted by a terminal phenyl group. All alkyl C-iminosugars displayed potent and selective inhibition towards β-glucosidase with IC50 values ranging from 0.15 to 68μM. Compound 10 with an 1-deoxynojirimycin backbone was the most active and was found to act as a competitive inhibitor with Ki=31nM, therefore emerging as one of the most potent inhibitor of β-glucosidase reported to date. Inhibition of β-mannosidase was observed with compounds 1, 3, 7 and 10, but only weak inhibition could be detected with the alkyl-C-iminosugars on the other tested glycosidases (α-glucosidase, α-fucosidase, α- and β-galactosidase).
authors.affiliation: ICMR-UMR CNRS 7312, Groupe Isolement et Structure, Campus Sciences, Bat. 18, BP 1039, 51687 Reims Cedex 2, France; Laboratoire de Chimie Organique Biologique, 01 BPV 34 Abidjan 01, Université Félix-Houphouët Boigny d'Abidjan-Cocody, Côte d'Ivoire.
authors.forename: Diane Patricia Apie
authors.initials: DP
authors.lastname: Gossan
authors.affiliation: ICMR-UMR CNRS 7312, Groupe Isolement et Structure, Campus Sciences, Bat. 18, BP 1039, 51687 Reims Cedex 2, France. Electronic address: abdulmagid.alabdulmagid@univ-reims.fr.
authors.forename: Abdulmagid
authors.initials: A
authors.lastname: Alabdul Magid
authors.affiliation: Laboratoire de Chimie Organique Biologique, 01 BPV 34 Abidjan 01, Université Félix-Houphouët Boigny d'Abidjan-Cocody, Côte d'Ivoire.
authors.forename: Philomène Akoua
authors.initials: PA
authors.lastname: Kouassi-Yao
authors.affiliation: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, UFR Sciences Exactes et Naturelles, BP 1039, 51687 Reims Cedex 2, France.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Behr
authors.affiliation: Laboratoire de Chimie Organique Biologique, 01 BPV 34 Abidjan 01, Université Félix-Houphouët Boigny d'Abidjan-Cocody, Côte d'Ivoire.
authors.forename: Antoine Coffy
authors.initials: AC
authors.lastname: Ahibo
authors.affiliation: Laboratoire de Chimie Organique Biologique, 01 BPV 34 Abidjan 01, Université Félix-Houphouët Boigny d'Abidjan-Cocody, Côte d'Ivoire.
authors.forename: Léon Atoutou
authors.initials: LA
authors.lastname: Djakouré
authors.affiliation: Service Commun d'Analyses, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, Bat. 18, BP 1039, 51687 Reims Cedex 2, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Harakat
authors.affiliation: ICMR-UMR CNRS 7312, Groupe Isolement et Structure, Campus Sciences, Bat. 18, BP 1039, 51687 Reims Cedex 2, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Voutquenne-Nazabadioko
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D050111:Imino Sugars / Q000737:chemistry* / Q000302:isolation & purification; D020128:Inhibitory Concentration 50; D019660:Malvaceae / Q000737:chemistry*; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D050111:Imino Sugars; C000598223:glyphaeaside C; D006026:Glycoside Hydrolases
keywords: Glycosidases inhibition; Glyphaea brevis; Iminosugars; Malvaceae; Nojirimycins