title: Selenoureido-iminosugars: A new family of multitarget drugs.
abstract: 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 tackling simultaneously the Gaucher disease (by selective inhibition of β-glucosidase, Ki = 1.6-5.5 μM, with improved potency and selectivity compared to deoxynojirimycin) and its neurological complications (by inhibiting AChE, Ki up to 5.8 μM). Moreover, an excellent mimicry of the selenoenzyme glutathione peroxidase was also found for the catalytic scavenging of H2O2 (Kcat/Kuncat 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.
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, 41071 Seville, Spain.
authors.forename: Jacob Ingemar
authors.initials: JI
authors.lastname: Olsen
authors.affiliation: BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, c/ Astrofísico Francisco Sánchez 2, E-38206 La Laguna, Spain.
authors.forename: Gabriela B
authors.initials: GB
authors.lastname: Plata
authors.affiliation: BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, c/ Astrofísico Francisco Sánchez 2, E-38206 La Laguna, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, 41071 Seville, Spain. Electronic address: osc-lopez@us.es.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: López
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark.
authors.forename: Mikael
authors.initials: M
authors.lastname: Bols
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, 41071 Seville, Spain.
authors.forename: José G
authors.initials: JG
authors.lastname: Fernández-Bolaños
mesh_terms: D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000187:drug effects; D000478:Alkylation; D044602:Cellulases / Q000037:antagonists & inhibitors; D015195:Drug Design; D005776:Gaucher Disease / Q000188:drug therapy*; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors; D006801:Humans; D050111:Imino Sugars / Q000737:chemistry* / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D050111:Imino Sugars; D016566:Organoselenium Compounds; C501633:deoxynojirimycine; D017485:1-Deoxynojirimycin; D005979:Glutathione Peroxidase; D000110:Acetylcholinesterase; D044602:Cellulases; D005944:Glucosamine
keywords: AChE inhibition; Antioxidant; GPx mimic; Glycosidase inhibition; Iminosugars; Selenoureas