Rational Design, Synthesis, and Biological Investigations of N-Methylcarbamoylguanidinyl Azamacrolides as a Novel Chitinase Inhibitor

文献类型： 外文期刊

第一作者： Zhao, Zhixiang

作者： Zhao, Zhixiang;Xu, Qingbo;Wang, Siming;Dong, Yanhong;Zhang, Jianjun;Chen, Wei;Yang, Qing;Chen, Wei;Yang, Qing

作者机构：

关键词： chitinase; Argifin; inhibitor; azamacrolide; insecticide

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.895； 五年影响因子：6.048 ）

ISSN： 0021-8561

年卷期： 2022 年 70 卷 16 期

页码：

收录情况： SCI

摘要： Chitinase is one of the most important glycoside hydrolyases, widely existing in bacteria, fungi, insects, and plants. It is involved in fungal cell wall remodeling and insect molting. Chitinase inhibitors are an effective means of controlling pathogens and pests. Natural product argifin is a 17-membered pentapeptide that exhibits efficient chitinase inhibitory activity. However, the complexity of the synthetic process results in a lot of restrictions for wide range of applications. In this work, we designed a series of azamacrolide chitinase inhibitors based on the structural features of argifin that have high inhibitory activities against bacterial and insectile chitinase. The most potent chitinase inhibitor compound 19c exhibited IC50 values of 56 nM and 110 nM against Of Chi-h and SmChiB, respectively. The molecular docking and molecular dynamics simulations revealed that all inhibitors were bound to the -1 subsite of chitinases via N-methylcarbamoylguanidinyl as well as argifin. Finally, a bioactivity assay against pests was carried out. Compound 18a showed 80% mortality for Mythimna separata at a concentration of 50 mg/L. Besides, insecticides 19b and 19c exhibited high mortality against Plutella xylostella (76 and 73% mortalities at 50 mg/L, respectively).

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[1]Rational Design, Synthesis, and Biological Investigations of N-Methylcarbamoylguanidinyl Azamacrolides as a Novel Chitinase Inhibitor. Zhao, Zhixiang,Xu, Qingbo,Wang, Siming,Dong, Yanhong,Zhang, Jianjun,Chen, Wei,Yang, Qing,Chen, Wei,Yang, Qing. 2022

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