Selenoureido-iminosugars: A new family of multitarget drugs

Herein we report the synthesis of N-alkylated deoxynojirimycin derivatives decorated with a selenoureido motif at the hydrocarbon tether as an example of unprecedented multitarget agents. Title compounds were designed as dual drugs for taclding simultaneously the Gaucher disease (by selective inhibition of beta-glucosidase, K-i = 1.6-5.5 mu M, with improved potency and selectivity compared to deoxynojirimycin) and its neurological complications (by inhibiting AChE, K-i up to 5.8 mu M). Moreover, an excellent mimicry of the selenoenzyme glutathione peroxidase was also found for the catalytic scavenging of H2O2 (K-cat/K-uncat up to 640) using PhSH as a cofactor, with improved activity compared to known positive controls, like (PhSe)(2) and ebselen; therefore, such compounds are also excellent scavengers of peroxides, an example of reactive oxygen species present at high concentrations in patients of Gaucher disease and neurological disorders. (C) 2016 Elsevier Masson SAS. All rights reserved.