文献类型：期刊文献

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

作者：Zhu, Ling[1];Chen, Lei[2,3];Shao, Xusheng[1,4];Cheng, Jiagao[1];Yang, Qing[2,3];Qian, Xuhong[1,5]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing 100193, Peoples R China;[3]Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Guangdong Lab Lingnan Modern Agr, Shenzhen Branch, Shenzhen 518120, Peoples R China;[4]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China

年份：2021

卷号：69

期号：27

起止页码：7526

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20213010671958);WOS:【SCI-EXPANDED(收录号:WOS:000674324600001)】；

基金：This work was financially supported by the Key Project of the Shanghai Science and Technology Committee (no. 18DZ1112703), the National Natural Science Foundation of China (nos. 31830076 and 21977030), and the Shenzhen Science and Technology Program (no. KQTD20180411143628272).

语种：英文

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

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.