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Discovery of diphenyl ethers as novel inhibitors of insect trehalase via virtual screening and biological assaysqrcode

Dec. 23, 2024

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Dec. 23, 2024

Trehalase hydrolyzes trehalose to glucose to provide energy for insects or building blocks for chitin synthesis. Because trehalase is critical to insects but not to humans, it has long been considered a promising target for green insecticides. However, the known trehalase inhibitors are mainly sugar derivatives with poor druggability. 


In this study, the trehalase from Ostrinia furnacalis (OfTreh) was expressed and characterized. By integrative computational strategies, diphenyl ether herbicides were discovered as the first non-carbohydrate inhibitors of insect trehalases. Bifenox and its more stable derivative, chlomethoxyfen, inhibited OfTreh with Ki values of 56 and 43 μM, respectively. The oral administration of bifenox or chlomethoxyfen to locusts resulted in the inhibition of trehalose hydrolysis in vivo, leading to a mortality rate of 66% and server locomotion disorder in the survivors. 


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This study not only established a platform for the development of insecticides targeting trehalase but also discovered a new mechanism for diphenyl ethers to kill insects as trehalase inhibitors.


Learn more at ScienceDirect.

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