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Small-molecule inhibitors of insect chitinolytic enzymes are potential insecticides. However, the reported inhibitors that target one enzyme usually exhibit unsatisfactory bioactivity. On the basis of the multitarget strategy, we performed a high-throughput screening of a natural product library to find insecticide leads against four chitinolytic enzymes from the Asian corn borer Ostrinia furnacalis (OfChtI, OfChtII, OfChi-h, and OfHex1). Several phytochemicals were discovered to be multitarget inhibitors of these enzymes and were predicted to occupy the -1 substrate-binding subsite and engage in polar interactions with catalytically important residues. Shikonin and wogonin, which had good inhibitory activities toward all four enzymes, also exhibited significant insecticidal activities against lepidopteran agricultural pests. This study provides the first example of using a multitarget high-throughput screening strategy to exploit natural products as insecticide leads against chitin biodegradation during insect molting.


Wenqin Li, Yi Ding, Huitang Qi, Tian Liu, Qing Yang. Discovery of Natural Products as Multitarget Inhibitors of Insect Chitinolytic Enzymes through High-Throughput Screening. Journal of agricultural and food chemistry. 2021 Sep 22;69(37):10830-10837

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PMID: 34496207

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