Virtual screening identifies a novel piperazine-based insect juvenile hormone agonist

Area of Science:

• Agrochemistry
• Computational Chemistry
• Entomology

Background:

• Juvenile hormone (JH) agonists are crucial insect growth regulators for pest management.
• Discovering novel JH agonists with unique structures is essential for overcoming resistance and improving efficacy.

Purpose of the Study:

• To identify novel juvenile hormone (JH) agonists through a multi-step virtual screening process.
• To find compounds with potential for development into new insect pest management tools.

Main Methods:

• Utilized a multi-step virtual screening of 5 million compounds.
• Employed shape/chemical similarity, molecular docking against the Drosophila methoprene-tolerant receptor, and MM/PBSA free energy calculations.
• Validated 11 candidates via a luciferase reporter assay.

Main Results:

• Identified one hit compound containing a piperazine ring system with an EC50 of 870 nM.
• The identified compound is structurally dissimilar to known JH agonists.
• The hit compound is synthetically accessible, indicating ease of further development.

Conclusions:

• The novel piperazine-containing compound is a promising lead for developing new JH agonists.
• This discovery provides a new structural class for insect growth regulator research.
• The findings support the use of computational screening for novel agrochemical discovery.