Novel Inhibitors of an Insect Pest Chitinase: Design and Optimization of 9-O-Aromatic and Heterocyclic Esters of Berberine

文献类型： 外文期刊

第一作者： Zhu, Ling

作者： Zhu, Ling;Shao, Xusheng;Cheng, Jiagao;Qian, Xuhong;Chen, Lei;Yang, Qing;Chen, Lei;Yang, Qing;Shao, Xusheng;Qian, Xuhong

作者机构：

关键词： Of Chi-h; chitinase; glycoside hydrolase; inhibitor; berberine; pesticide

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.279； 五年影响因子：5.269 ）

ISSN： 0021-8561

年卷期： 2021 年 69 卷 27 期

页码：

收录情况： SCI

摘要： OfChi-h, a lepidopteran-exclusive glycoside hydrolase family 18 (GH18) chitinase from the agricultural insect pest Ostrinia furnacalis, is a promising molecular target candidate for pest control and management. Berberine (BER), a traditional Chinese medicine, binds to a wide variety of glycosyl hydrolases via an identical mechanism, showing potential as a pesticide lead compound. In this work, we found that BER was a moderate inhibitor of OfChi-h with a Ki of 16.1 mu M. To improve its efficacy, a series of BER derivatives featuring an ester bond linked to an aromatic or heterocyclic aromatic ring at the 9-position were designed and evaluated as effective OfChi-h inhibitors. The most potent compound, compound 19e with a nicotinate group, exhibited a Ki of 0.093 mu M. Molecular docking analysis suggested that the common binding mode of BER derivatives featured a network of pi-pi stacking and electrostatic interactions and that the group at the 9-position enhanced the van der Waals and hydrogen bonding interactions. Administration of the BER derivative 19c to 4th-instar O. furnacalis larvae in an artificial diet led to their impaired growth and metamorphosis. This work provides a new starting point for the modification of BER for use in pest control.

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