Insect chitinolyticβ-N-acetyl-D-hexosaminidase,such as OfHex1 from Ostrinia furnacalis,is a potential target for insecticide design.Among the known OfH ex1 inhibitors,Q2 is of great interest because it is the first n...Insect chitinolyticβ-N-acetyl-D-hexosaminidase,such as OfHex1 from Ostrinia furnacalis,is a potential target for insecticide design.Among the known OfH ex1 inhibitors,Q2 is of great interest because it is the first non-carbohydrate inhibitor.In this study,we designed and synthesized a series of Q2 derivatives by replacing the thiadiazole and naphthalimide groups and changing the linker length.Compound 3 m showed the best inhibitory activity with a Kivalue of 0.34 mmol/L against OfHex1,which is about onequarter that of Q2(K_i=1.4 mmol/L).Compound 6 a showed the best inhibitory activity among the quinoline-containing derivatives(K_i=2.3 mmol/L).Molecular docking indicated that although 3 m,6 a,and Q2 binding the active pocket of OfHex1 in similar mode,compound 3 m engaged better than the other compounds in intermolecular interaction with OfH ex1.展开更多
基金the National Key Research and Development Program of China(Nos.2017YFD0200500,2017YFD0201400,2018YFD0200100)the National Natural Science Foundation of China(No.31871959)for the financial support
文摘Insect chitinolyticβ-N-acetyl-D-hexosaminidase,such as OfHex1 from Ostrinia furnacalis,is a potential target for insecticide design.Among the known OfH ex1 inhibitors,Q2 is of great interest because it is the first non-carbohydrate inhibitor.In this study,we designed and synthesized a series of Q2 derivatives by replacing the thiadiazole and naphthalimide groups and changing the linker length.Compound 3 m showed the best inhibitory activity with a Kivalue of 0.34 mmol/L against OfHex1,which is about onequarter that of Q2(K_i=1.4 mmol/L).Compound 6 a showed the best inhibitory activity among the quinoline-containing derivatives(K_i=2.3 mmol/L).Molecular docking indicated that although 3 m,6 a,and Q2 binding the active pocket of OfHex1 in similar mode,compound 3 m engaged better than the other compounds in intermolecular interaction with OfH ex1.
