A second-generation ferrocene-iminosugar hybrid with improved fucosidase binding properties.
Fiche publication
Date publication
mars 2016
Journal
Bioorganic & medicinal chemistry letters
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DUCA Laurent
Tous les auteurs :
Hottin A, Scandolera A, Duca L, Wright DW, Davies GJ, Behr JB
Lien Pubmed
Résumé
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.
Mots clés
Animals, Antineoplastic Agents, chemical synthesis, Bacteroides, enzymology, Binding Sites, drug effects, Cattle, Cell Line, Tumor, Cell Proliferation, drug effects, Cell Survival, drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Enzyme Inhibitors, chemical synthesis, Ferrous Compounds, chemistry, Humans, Imino Sugars, chemistry, Kidney, enzymology, Molecular Structure, Structure-Activity Relationship, alpha-L-Fucosidase, antagonists & inhibitors
Référence
Bioorg. Med. Chem. Lett.. 2016 Mar;26(6):1546-9