Thiazolylhydrazone dervatives as inhibitors for insect N-acetyl-β-D-hexosaminidase and chitinase

Insect chitinase and N-acetyl-β-D-hexosaminidases (Hex) are potential targets for developing new pesticides. Here, a series of thiazolylhydrazones I (with substituted group R₁ at N3) and II (with substituted group R₁ at N2) were designed, synthesised and evaluated as competitive inhibitors of OfHex1 and OfChi-h, from the agricultural pest Ostrinia furnacalis. Derivatives I-3d and II-3d, with phenoxyethyl group at R₁, demonstrated the best inhibitory activities against OfHex1 and OfChi-h. Molecular docking analysis indicated that the branched conformation compound II-3d (K_i = 1.5 μmol/L) formed more hydrogen bonds with OfHex1 than the stretched conformation compound I-3d (K_i = 5.9 μmol/L). The differences in compounds’ binding conformations with OfChi-h explained differences in inhibitory activity of compounds I-3d (K_i = 1.9 μmol/L) and II-3d (K_i = 4.1 μmol/L). This work suggests a novel scaffold for developing specific Hex and Chi-h inhibitors.