Rational Design and Identification of Novel Piperine Derivatives as Multichitinase Inhibitors

Area of Science:

• Agricultural Entomology
• Biochemistry
• Medicinal Chemistry

Background:

• The Asian corn borer (Ostrinia furnacalis) is a major agricultural pest.
• Chitinases OfChtI, OfChtII, and OfChi-h are key targets for pest control agents.
• Piperine shows initial inhibitory effects on these chitinases.

Purpose of the Study:

• To design and synthesize novel piperine derivatives as multichitinase inhibitors.
• To evaluate the insecticidal activity of these derivatives against O. furnacalis.
• To elucidate the molecular mechanism of inhibition.

Main Methods:

• Rational design of piperine derivatives based on conserved chitinase residues.
• Chemical synthesis of 19 novel compounds.
• In vitro enzyme inhibition assays and insecticidal activity testing.
• Molecular docking and microinjection experiments.

Main Results:

• Piperine derivatives were synthesized, with Compound 5k showing the highest inhibitory activity (K = 11.78–22.82 μM).
• Compound 5k exhibited superior insecticidal efficacy against O. furnacalis compared to single- or dual-target inhibitors.
• Molecular studies revealed Compound 5k binds to conserved TRP and TYR residues via hydrogen bonds, hydrophobic, and π-π interactions.
• Microinjection demonstrated Compound 5k induces sublethal effects by disrupting growth and development.

Conclusions:

• Compound 5k is a potent multichitinase inhibitor with significant insecticidal activity against O. furnacalis.
• The study validates multichitinase inhibitors as a promising approach for controlling O. furnacalis.
• Piperine derivatives represent a new class of agrochemicals for pest management.