Self-assembled multivalent glycosidase inhibition effect based on perylene monoimide-deoxynojirimycin conjugates

Abstract

Diabetes mellitus is a serious and chronic disease. Recently, multivalent glycosidase inhibitors were found and rapidly developed. The key element for construction of multivalent glycosidase inhibitor remained a large challenge. In this paper, a perylene monoimide derivative (PMI-DNJ) with 1-deoxynojirimycin conjugated was synthesized. Furthermore, its self-assembly behaviors and glycosidase inhibition effects were studied. PMI-DNJ showed very good glycosidase inhibition activity against α-mannosidase (jack bean) with a Ki value of 1.41 μM, increased approximately 24-fold and 65-fold compared with the control drugs (miglitol and DNJ-1). Moreover, the Ki value of PMI-DNJ against α-glucosidase was 10.98 μM, increased approximately 1.88-fold and 5.6-fold compared with the control drugs (miglitol and DNJ-1). In addition, PMI-DNJ exhibited potent hypoglycemic effects in mice with 27.36% and 30.08 % decreases in blood glucose under the drug dose of 0.5 and 1.0 mg/kg. This work introduced a new means to develop antihyperglycemic agents in the field of multivalent glycomimetics.