New synthetic seven-membered 1-azasugars displaying potent inhibition towards glycosidases and glucosylceramide transferase

Chembiochem : a European Journal of Chemical Biology
Hongqing LiYves Blériot

Abstract

Several members of a new family of seven-membered azasugars, which can be seen as 1-azasugar ring homologues, have been obtained by simple chemical transformations starting from a sugar-derived azidolactol. Unlike their piperidine counterparts, these molecules are chemically stable when they possess a hydroxy group at the pseudo-C-2 position. Biological assays with a range of carbohydrate-processing enzymes have revealed interesting potential for these compounds. A trihydroxymethyl-substituted azepane displayed strong competitive inhibition on almond beta-glucosidase (K(i)=2.5 microM) while a trihydroxylated carboxylic acid derivative proved to be a potent and selective L-fucosidase inhibitor (K(i)=41 nM). N-Butylation of these seven-membered 1-azasugars generated derivatives with some activity towards the Gaucher's disease-related glucosylceramide transferase (IC(50) 75 microM) that did not interact significantly with digestive glucosidases.

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Citations

Feb 24, 2009·Glycoconjugate Journal·Terry D ButtersYves Blériot
Aug 2, 2011·Beilstein Journal of Organic Chemistry·Ileana DragutanAlbert Demonceau
Oct 29, 2009·Angewandte Chemie·Tom WennekesJohannes M F G Aerts
Sep 6, 2011·Bioorganic & Medicinal Chemistry·Amit M JabgundeDilip D Dhavale
Dec 15, 2010·Carbohydrate Research·Tzenge-Lien ShihChun-Hung Lin
Oct 27, 2009·Bioorganic & Medicinal Chemistry Letters·Martijn D P RisseeuwHerman S Overkleeft
Dec 3, 2014·Bioorganic Chemistry·Hanaa TaghzoutiRichard Plantier-Royon
Nov 26, 2015·Acta Crystallographica. Section E, Crystallographic Communications·Alpesh Ramanlal PatelFei Liu
May 10, 2013·Organic & Biomolecular Chemistry·Alpesh Ramanlal PatelFei Liu
Apr 23, 2011·Organic & Biomolecular Chemistry·Nicolas Ardes-GuisotBoris Vauzeilles
Oct 24, 2012·Organic & Biomolecular Chemistry·Mallikharjuna Rao LSubhash Chandra Taneja
Apr 22, 2021·Organic & Biomolecular Chemistry·Irene Conforti, Alberto Marra
Feb 10, 2011·ACS Medicinal Chemistry Letters·Amar GhisaidoobeRichard J B H N van den Berg

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