Triazinobenzoxazepine Derivatives Identified as Dual-Chitinase Inhibitors to Regulate Insect Growth

Area of Science:

• Agricultural Science
• Biochemistry
• Computational Chemistry

Background:

• Chitin metabolism is a key target for selective pesticide development.
• Existing chitinase inhibitors lack optimal efficacy and specificity.
• Computer-aided strategies are needed for novel agrochemical discovery.

Purpose of the Study:

• To discover novel dual-target chitinase inhibitors using virtual screening.
• To identify potent triazinobenzoxazepine derivatives (TBZs) for insect control.

Main Methods:

• Dual-target virtual screening of triazinobenzoxazepine derivatives.
• In vitro enzyme inhibition assays against O. furnacalis chitinases (OfChi-h, OfChtI).
• Insecticidal activity testing against Ostrinia furnacalis and Plutella xylostella.
• Mechanism elucidation using electron microscopy and DFT/ESP calculations.

Main Results:

• Compound TBZ-15 exhibited potent dual inhibition of OfChi-h (Ki=0.64 μM) and OfChtI (Ki=0.43 μM).
• TBZ-4 and TBZ-15 demonstrated superior insecticidal activity compared to hexaflumuron.
• TBZ-4 showed enhanced control efficacy over chlorbenzuron.
• Toxicity predictions indicated safety for non-target organisms.

Conclusions:

• Triazinobenzoxazepine derivatives (TBZs) are effective eco-friendly insecticides.
• Computer-aided drug design accelerates the development of sustainable agrochemicals.
• Targeting insect chitin metabolism offers a promising strategy for pest management.