Improving the Insecticidal Activity of Diamides via 3D-QSAR Hydrophobic Field Optimization

Guided by a 3D-QSAR hydrophobic field model, a series of ether-linked anthranilic diamides were synthesized for insecticidal screening. Bioassays identified that compounds N01 and N03 exhibited insecticidal activities against Mythimna separata with the LC₅₀ of 0.23 and 0.20 mg·L^-1, respectively. As compared with chlorantraniliprole, N01 demonstrated over 3-fold of significantly enhanced higher potency against Plutella xylostella with an LC₅₀ of 5.0 × 10^-4 mg·L^-1 and 1.6 × 10^-3 mg·L^-1, respectively. N01 showed safety to Apis mellifera and Danio rerio and lower toxicity to HEK293 cells. Transcriptomic and qRT-PCR analyses confirmed both N01 and chlorantraniliprole upregulate RyR gene expression in P. xylostella. Unlike chlorantraniliprole, N01 did not activate the insect resistance of Brassica oleracea var.botrytis Linnaeus, and its efficacy was mainly contributed to its physicochemical properties. Molecular docking and dynamics simulations demonstrated that N01 forms a more stable binding mode with P. xylostella RyR. The results showed that N01 is a promising high-efficacy insecticidal candidate.