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

Area of Science:

• Agricultural Chemistry
• Organic Chemistry
• Molecular Biology

Background:

• Development of novel insecticides is crucial for sustainable agriculture and pest management.
• Existing insecticides face challenges including resistance development and environmental impact.
• Anthranilic diamides represent a class of insecticides with potential for new lead discovery.

Purpose of the Study:

• To design and synthesize novel ether-linked anthranilic diamides guided by 3D-QSAR.
• To evaluate the insecticidal activity and safety profile of synthesized compounds.
• To elucidate the molecular mechanism of action for promising candidates.

Main Methods:

• 3D-QSAR hydrophobic field modeling for rational design.
• Synthesis of a series of ether-linked anthranilic diamides.
• Bioassays for insecticidal activity against Mythimna separata and Plutella xylostella.
• Toxicity assessments on non-target organisms (Apis mellifera, Danio rerio) and cell lines (HEK293).
• Transcriptomic and qRT-PCR analyses to investigate gene expression changes (RyR).
• Molecular docking and dynamics simulations to study binding interactions with target proteins.

Main Results:

• Compounds N01 and N03 exhibited potent insecticidal activity against Mythimna separata (LC50 0.23 and 0.20 mg·L−1).
• N01 demonstrated over 3-fold enhanced potency against Plutella xylostella compared to chlorantraniliprole (LC50 5.0 × 10−4 mg·L−1).
• N01 showed safety towards Apis mellifera, Danio rerio, and HEK293 cells.
• Both N01 and chlorantraniliprole upregulated RyR gene expression in P. xylostella.
• N01 did not induce insect resistance in Brassica oleracea var. botrytis and exhibited favorable physicochemical properties.
• Molecular simulations indicated a more stable binding mode of N01 with P. xylostella RyR.

Conclusions:

• Compound N01 is a highly effective and promising insecticidal candidate with a favorable safety profile.
• The physicochemical properties of N01 contribute significantly to its efficacy.
• N01 represents a potential alternative to existing insecticides, with a novel binding interaction with RyR.
• Further research into N01 could lead to the development of new pest management strategies.