Linear Peptidomimetics Containing Isoxazoline Scaffold: Design, Synthesis, Bioevaluation as Efficient Insecticidal...

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Agricultural Science

Background:

• Peptidomimetics offer diverse structural possibilities for bioactive molecule development.
• Lepidopteran pests pose significant threats to global agriculture, necessitating novel control strategies.
• Existing insecticides face challenges due to resistance and environmental concerns.

Purpose of the Study:

• To design and synthesize novel polysubstituted linear peptidomimetics incorporating arylisoxazoline heterocycles.
• To evaluate the insecticidal activity of these novel compounds against key lepidopteran pests.
• To investigate the potential mechanism of action, specifically targeting the γ-aminobutyric acid (GABA) receptor.

Main Methods:

• A four-component, one-pot synthesis utilizing green chemistry principles.
• Structural elucidation using spectroscopic techniques (¹H NMR, ¹³C NMR, ESI-MS).
• Bioassays against *Plutella xylostella* and *Helicoverpa armigera* larvae, comparing with standard insecticides.
• Computational studies including Density Functional Theory (DFT) and molecular docking.

Main Results:

• Successful synthesis of structurally novel peptidomimetics.
• Most compounds displayed significant insecticidal activity against tested lepidopteran pests at 100 μg/mL.
• Compound JK-10 exhibited excellent efficacy, achieving 100% larval mortality at 0.195 μg/mL, outperforming Chlorantraniliprole.
• DFT and docking studies indicated strong binding affinity to the GABA receptor.

Conclusions:

• The synthesized arylisoxazoline-hybridized peptidomimetics represent a promising new class of insecticides.
• Compound JK-10 is a potent lead candidate for developing novel GABA receptor inhibitors.
• These findings support the potential of these compounds for integrated pest management strategies in agriculture.