α-L-fucosidase inhibition by pyrrolidine-ferrocene ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
α-L-fucosidase inhibition by pyrrolidine-ferrocene hybrids: rationalization of ligand-binding properties by structural studies
Auteur(s) :
Hottin, Audrey [Auteur]
Wright, Daniel W [Auteur]
Steenackers, Agata [Auteur]
Delannoy, Philippe [Auteur]
Dubar, Faustine [Auteur]
Biot, Christophe [Auteur]
Davies, Gideon J [Auteur]
Behr, Jean-Bernard [Auteur]
Wright, Daniel W [Auteur]
Steenackers, Agata [Auteur]
Delannoy, Philippe [Auteur]
Dubar, Faustine [Auteur]
Biot, Christophe [Auteur]
Davies, Gideon J [Auteur]
Behr, Jean-Bernard [Auteur]
Titre de la revue :
Chemistry (Weinheim an der Bergstrasse, Germany)
Nom court de la revue :
Chemistry
Numéro :
19
Pagination :
9526-9533
Date de publication :
2013-07-15
ISSN :
1521-3765
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the ...
Lire la suite >Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the synthesis of a new series of pyrrolidine-ferrocene conjugates, consisting of a L-fuco-configured dihydroxypyrrolidine as the fucosidase ligand armed with a cytotoxic ferrocenylamine moeity. Three-dimensional structures of several of these fucosidase inhibitors reveal transition-state-mimicking (3)E conformations. Elaboration with the ferrocenyl moiety results in sub-micromolar inhibitors of both bovine and bacterial fucosidases, with the 3D structure of the latter revealing electron density indicative of highly mobile alkylferrocene compounds. The best compounds show a strong antiproliferative effect, with up to 100% inhibition of the proliferation of MDA-MB-231 cancer cells at 50 μM.Lire moins >
Lire la suite >Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the synthesis of a new series of pyrrolidine-ferrocene conjugates, consisting of a L-fuco-configured dihydroxypyrrolidine as the fucosidase ligand armed with a cytotoxic ferrocenylamine moeity. Three-dimensional structures of several of these fucosidase inhibitors reveal transition-state-mimicking (3)E conformations. Elaboration with the ferrocenyl moiety results in sub-micromolar inhibitors of both bovine and bacterial fucosidases, with the 3D structure of the latter revealing electron density indicative of highly mobile alkylferrocene compounds. The best compounds show a strong antiproliferative effect, with up to 100% inhibition of the proliferation of MDA-MB-231 cancer cells at 50 μM.Lire moins >
Langue :
Anglais
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
Régulation de la glycosylation terminale
Glycobiologie structurale des interactions hôtes-pathogènes
Glycobiologie structurale des interactions hôtes-pathogènes
Date de dépôt :
2020-02-12T15:11:08Z