Study on the Synthesis and Biological Activities of N-Alkylated Deoxynojirimycin Derivatives with a Terminal Tertiary Amine

Abstract

A series of N-alkylated deoxynojirimycin (DNJ) derivatives connected to a terminal tertiary amine at the alkyl chains of various lengths were prepared. These novel synthetic compounds were assessed for preliminary glucosidase inhibition and anticancer activities in vitro. Potent and selective inhibition was observed among them. Compound 7d (IC₅₀ = 0.052 mM) showed improved and selective inhibitory activity against β-glucosidase compared to DNJ (IC₅₀ = 0.65 mM). In addition, analysis of the kinetics of enzyme inhibition by using Lineweaver–Burk plots indicated that 7d inhibited β-glucosidase in a competitive manner, suggesting that 7d was expected to bind to the active site of β-glucosidase. Compounds 8b and 8c were found to be moderate and selective inhibitors of α-glucosidase. Nevertheless, none of compounds inhibited the growth of B16F10 melanoma cells.