Synthesis, glycosidase inhibitory activity and computational studies of dideoxymethylnojirimycin and its derivatives

Abstract

We report here the synthesis and biological evaluation of dideoxynojirimycin and its analogs and their functional effect on glucosidase enzyme inhibition against α-glucosidase(yeast), α-galactosidase and β-galactosidase (kluyveromyces lactis). All the compounds significantly inhibited the α-glucosidase(yeast) activity when compared to DNJ and shown strong inhibition against β-galactosidase (kluyveromyces lactis) when compared to DNJ. The molecular docking studies also reveals that these compounds showing strong ligand binding energies against yeast-ɑ-glucosidase- I, yeast β-galactosidase and human lysosomal acid–ɑ-glucosidase. Interestingly the analogues having N-H, N-alkyl and N-benzyl group along with ethyl group significantly inhibited the β-galactosidase activity when compared to DNJ. The in-silico studies are in correlation with invitro activity data; therefore, this study will be useful to develop further glycosidase inhibitors.

Keywords

• Dideoxymethylnojirimycin
• Glycosidase inhibitory activity
• Molecular docking