title: Synthesis of N-alkylated noeurostegines and evaluation of their potential as treatment for Gaucher's disease.
abstract: The potent and selective inhibitor of β-glucosidases, noeurostegine, was evaluated as an inhibitor of glucocerebrosidase (GCase) to give an IC(50) value of 0.4 μM, being 250- and 150-fold better than N-butyl and N-nonyl noeurostegine, respectively. The parent noeurostegine and its N-butyl and N-nonyl alkylated congeners were also tested as pharmacological chaperones against a N370S GCase mutant. Of these, only noeurostegine, was found to increase enzyme activity, which in potency was comparable to that previously reported for isofagomine.
authors.affiliation: Department of Chemistry, Aarhus University, Aarhus C, Denmark.
authors.forename: Tina S
authors.initials: TS
authors.lastname: Rasmussen
authors.forename: Sarah
authors.initials: S
authors.lastname: Allman
authors.forename: Gabriele
authors.initials: G
authors.lastname: Twigg
authors.forename: Terry D
authors.initials: TD
authors.lastname: Butters
authors.forename: Henrik H
authors.initials: HH
authors.lastname: Jensen
mesh_terms: D057075:Enzyme Assays; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D009662:Nortropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D009662:Nortropanes; C547946:noeurostegine; D005962:Glucosylceramidase