Synthetic deoxynojirimycin derivatives bearing a thiolated, fluorinated or unsaturated N-alkyl chain: identification of potent α-glucosidase and trehalase inhibitors as well as F508del-CFTR correctors.
Org Biomol Chem
; 13(43): 10734-44, 2015 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-26356422
ABSTRACT
The synthesis of eleven 1-deoxynojirimycin (DNJ) derivatives presenting either a monofluoro, difluoro, thiolated or unsaturated N-alkyl chain of various length is described. Exploiting the unsaturated moiety on the nitrogen, fluorine has been introduced through a HF/SbF5 superacid catalysed hydrofluorination and thiol-ene click chemistry allowed introduction of sulfur. The synthetic derivatives have been tested for their ability to inhibit glycosidases and correct F508del-CFTR. Two of the unsaturated iminosugars exhibited potency similar to Miglustat as F508del-CFTR correctors. The thioalkyl iminosugars as well as the corresponding alkyl iminosugars demonstrated low micromolar α-glucosidases and trehalases inhibition. Introduction of fluorine abolished F508del-CFTR correction and trehalase inhibition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trealase
/
1-Desoxinojirimicina
/
Regulador de Condutância Transmembrana em Fibrose Cística
/
Inibidores Enzimáticos
/
Inibidores de Glicosídeo Hidrolases
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article