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

Insect chitinolytic β-N-acetyl-D-hexosaminidase, such as OfHex1 from Ostrinia furnacalis, is a potential target for insecticide design. Among the known OfHex1 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 OfHex1, 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 OfHex1 in similar mode, compound 3m engaged better than the other compounds in intermolecular interaction with OfHex1.