Synthesis and glycosidase inhibiton of two types of N-alkylated 1-deoxynojirimycin derivatives
Abstract
The naturally occurring alkaloid 1-deoxynojirimycin (DNJ) represents a well-known and potent class of α-glucosidase inhibitors. In this study, two novel derivatives-butylguanidine-deoxynojirimycin 8 and glucose-deoxynojirimycin 9 were prepared and screened for their ability to inhibit glucosidase enzymes. Compound 8 (IC50 = 0.364 mM) was more active against α-glucosidase (yeast) than N-octyl-DNJ. Compound 9 (IC50 = 0.083 mM) exhibited up to nearly 2-fold inhibitory activity compared to DNJ (IC50 = 0.154 mM). Neither compound displayed significant inhibition toward β-glucosidase derived from almonds. Enzyme kinetics using Lineweaver-Burk analysis revealed that both derivatives act as competitive inhibitors. Molecular docking studies further confirmed that compounds 8 and 9 bind within the active site pocket of the target enzyme. The structure-activity relationships exhibited that inserting a guanidine group or introducing a sugar ring onto the N-alkyl chain of DNJ greatly influences α-glucosidase inhibitory activity.
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