Naphthalimide and quinoline derivatives as inhibitors for insect N-acetyl-β-d-hexosaminidase

Abstract Insect chitinolytic β - N -acetyl- d -hexosaminidase, such as Of Hex1 from Ostrinia furnacalis , is a potential target for insecticide design. Among the known Of Hex1 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 3m showed the best inhibitory activity with a K i value of 0.34 μmol/L against Of Hex1, which is about one-quarter that of Q2 ( K i  = 1.4 μmol/L). Compound 6a showed the best inhibitory activity among the quinoline-containing derivatives ( K i  = 2.3 μmol/L). Molecular docking indicated that although 3m , 6a , and Q2 binding the active pocket of Of Hex1 in similar mode, compound 3m engaged better than the other compounds in intermolecular interaction with Of Hex1.