Application of berberine and its derivatives as hexosaminidase inhibitors

Abstract

The invention discloses application of berberine and a derivative of the berberine as a hexosaminidase inhibitor. The general structure formula of the hexosaminidase inhibitor is shown as I or II; in all screened 35 compounds, the berberine and the derivative of the berberine show certain inhibition activity on hexosaminidase OfHex1; particularly, the suppression rate of Sysu-00021 and Sysu-00679 on the OfHex1 enzyme is respectively 76 percent and 79 percent, and the inhibition constant Ki is respectively 2mu M and 1.8mu M. Compound applicable object determination shows that under the final concentration of 10mu M, the compound shows higher inhibition activity on the hexosaminidase OfHex1; no inhibition activity is shown on the hexosaminidase HsHexB derived from the human. In a word, the berberine and the derivative of the berberine have wide application prospects in the fields of biology, chemicobiology and the like.

Description

technical field

[0001] The invention belongs to the field of biotechnology, and in particular relates to the application of alkaloids and derivatives thereof as hexosaminidase inhibitors. Background technique

[0002] Chitin is a natural linear linear polysaccharide with N-acetyl-β-D-glucosamine (GlcNAc) as the basic unit and connected by β-1,4 glycosidic bonds. As an important structural component, chitin is abundantly present in the cell walls of fungi and diatoms, the shells of mollusks, the egg shells of nematodes, and the exoskeletons of crustaceans and insects, and the dynamic balance of its synthesis and hydrolysis is crucial for these organisms. growth and development are extremely important. Insect N-acetyl-D-hexosaminidase Hex1 (N-acetyl-D-hexosaminidase) from the glycosyl hydrolase 20 family is an indispensable chitin hydrolase in insect molt and metamorphosis. Down-regulating or disturbing the expression level of Hex1 gene will lead to abnormal molting and deat...

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