Glycosidases are enzymes catalyzing the hydrolysis of glycosidic bonds in complex sugars. They take part in the biosynthesis of the oligosaccharide chains and quality control mechanisms in the endoplasmic reticulum of the N-linked glycoproteins. These enzymes are related to various diseases, including cancer, diabetes, and infection. Therefore, inhibition of glycosidases has a significant impact on quality control, maturation, transport, and secretion of glycoproteins. As well as they can alter cell-cell or cell-virus recognition processes.

PBI-6DNJ is a potent and orally active multivalent glycosidase inhibitor, with good hypoglycemic effects in mice.

PBI-6DNJ is a perylene bisimides-Deoxynojirimycin (DNJ) conjugate. It is designed from 1-DNJ which is first isolated from white mulberry root barks in 1976. The inhibitor can inhibit kinds of α-glucosidase, such as mice, aspergilcus niger, rice, and jack bean with K_is of 0.14, 18.88, 0.02, and 0.08 μM, respectively.  Moreover, PBI-6DNJ exhibits better α-glucosidases inhibition activity than Miglitol.

In hyperglycemic C57BL-6J mice, which are fed with 2 g/kg pure maltose, PBI-6DNJ (0.5, 1.0, and 2.0 mg/kg) reduces the levels of postprandial blood glucose (PBG). PBI-6DNJ displays good hypoglycemic effects after the first 15 min administration, with PBG levels reduced by 24.68%, 36.99%, and 40.40% at the dose of 0.5, 1.0, and 2.0 mg/kg, respectively.

Besides, PBI-6DNJ (2 mg/kg; PO; for 7 days) does not cause significant changes in other biochemical indexes, for instance, the morphology of hepatocytes, the levels of ALP, AST, and ALT. It indicates that PBI-6DNJ has good biocompatibility.

In conclusion, PBI-6DNJ is an excellent multivalent glycosidase inhibitor, possessing hypoglycemic effects and the potential to research diabetes.

Reference:

[1] Yang JX, et al. Eur J Med Chem. 2022 Jul 22;241:114621.