Exploring substituent diversity of deoxynojirimycin–triazole hybrid iminosugars: Discovery of potent glucosidase inhibitors

Abstract

A series of deoxynojirimycin-triazole hybrid iminosugars had been prepared and investigated against a panel of glucosidases. Compound 10f (IC₅₀ = 0.063 ± 0.006 mM) exhibited improved inhibitory potency against α-glucosidase compared to 1-deoxynojirimycin (IC₅₀ = 0.155 ± 0.015 mM). Moreover, analysis of the kinetics of enzyme inhibition by using Lineweaver–Burk plots indicated that 10f inhibited α-glucosidase in a competitive manner. Compound 10m displayed moderate inhibition of α-glucosidase and β-glucosidase. The structure-activity relationships indicated that the introduction of the phenyl group and the nature of 4-position substituents on the phenyl ring had significant effects on the glucosidase inhibitory potency of the compounds.

Graphical Abstract

Keywords:

• Competitive manner
• 1-deoxynojirimycin
• α-glucosidase
• iminosugars