RESUMO
In the course of chemical modification of alpha-fucosidase inhibitors of 5a-carba-fucopyranosylamine type, an N-dodecyl derivative of the enantiomer 6-deoxy-5a-carba-beta-D-galactopyranosylamine demonstrated very strong inhibition of beta-galactosidase and beta-glucosidase. This finding led us to synthesize corresponding 6-hydroxy compounds, in order to elucidate structure-activity relationships for inhibitors of this type. Among four N-alkyl-5a-carba-beta-D-galactopyranosylamines prepared, the N-octyl derivative could be demonstrated to possess moderate activity toward alpha- and beta-galactosidases, and beta-glucosidase.
Assuntos
Galactosamina/análogos & derivados , Glicosídeo Hidrolases/antagonistas & inibidores , Galactosamina/síntese química , Galactosamina/farmacologia , Concentração Inibidora 50 , Relação Estrutura-Atividade , beta-Galactosidase/antagonistas & inibidores , beta-Glucosidase/antagonistas & inibidoresRESUMO
Chemical modification of 5a-carba-beta-DL-fucopyranosylamine (3) generated six N-substituted derivatives 9a-f, among which N-octyl 9b, decyl 9c, and phenylbutyl ones 9f were found to be very strong beta-galactosidase as well as beta-glucosidase inhibitors. The inhibitory activity appeared attributable to D-enantiomers from biological assays of prepared L-enantiomers. Therefore, 6-deoxy-5a-carba-beta-D-galactopyranosylamine (D-3) might be a promising lead compound for further design of new carba sugar-type beta-galactosidase inhibitors.
