title: A second-generation ferrocene-iminosugar hybrid with improved fucosidase binding properties.
abstract: The synthesis and the biological evaluation of a new ferrocenyl-iminosugar conjugate designed for fucosidase inhibitory and anticancer activity is described. The compound showed strong affinity for fucosidase from bovine kidney (Ki=23 nM) and from Bacteroides thetaiotaomicron (Ki=150 nM), displaying a 10-fold tighter binding affinity for these enzymes than the previous analogs. The interaction pattern that improves binding has been evaluated through structural analysis of the inhibitor-enzyme complex. The ferrocenyl-iminosugar exhibits significant anticancer activity on MDA-MB-231 and SK-MEL28 cell lines at 100 μM.
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: Audrey
authors.initials: A
authors.lastname: Hottin
authors.affiliation: UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Scandolera
authors.affiliation: UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Duca
authors.affiliation: Structural Biology Laboratory Department of Chemistry, University of York, York YO10 5DD, UK.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Wright
authors.affiliation: Structural Biology Laboratory Department of Chemistry, University of York, York YO10 5DD, UK.
authors.forename: Gideon J
authors.initials: GJ
authors.lastname: Davies
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. Electronic address: jb.behr@univ-reims.fr.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Behr
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001439:Bacteroides / Q000201:enzymology; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D050111:Imino Sugars / Q000737:chemistry / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D000075163:Metallocenes; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D050111:Imino Sugars; D000075163:Metallocenes; D005644:alpha-L-Fucosidase; C004998:ferrocene
keywords: Anticancer; Ferrocene; Fucosidase; Iminosugars; Inhibitors