Exploring the N-terminus region： Synthesis, bioactivity and 3D-QSAR of allatostatin analogs as novel insect growth regulators

作     者：Meizi Wang Li Zhang Xianwei Wang Yun Ling Xiaoqing Wu Xinlu Li Yiduo Mi Xinling Yang 

作者机构：Deportment of Applied Chemistry College of Science China Agricultural University Beijing 100193 China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2018年第29卷第9期

页      面：1375-1378页

核心收录：

学科分类：090403[农学-农药学(可授农学、理学学位）] 09[农学] 0904[农学-植物保护] 

基　　金：financially supported by the National Natural Science Foundation of China(No.21372257) the grants from the National Key Research and Development Plan(No.2017YFD0200504) 

主　　题：Allatostatins Juvenile hormone IGRs AST analogs Synthesis 3D-QSAR 

摘      要：Allatostatins （ASTs）, a family of insect neuropeptide, can inhibit juvenile hormone （JH） biosynthesis by the corpora allata （CA） in Diploptera punctata, and therefore be regarded as potential leads for the discovery of new insect growth regulators （1GRs）. But several shortcomings, such as their sensitivity to peptidases and high cost, impeded their practical application in pest management. In order to discover new IGRs, one AST analog B1 possessing non-peptide group was discovered with high ability to inhibit JH biosynthesis in vitro （IC50： 0.09 μmol/L） in our previous studies. In the present work, two series of B1 analogs with different substituents on the N-terminus region were designed and synthesized. The result suggested that benzene showed better activity than other heterocycles, and the para-substitution on the benzene was beneficial for activity. Moreover, analogs with logP value over 2.0 exhibited good activity, which indicated the hydrophobicity is important to the bioactivity. Three dimension quantitative structure-activity relationship （3D-QSAR） studies were performed to highlight the structural require- ments of ASTanalogs, which demonstrated introduction of bulkier substituents on the N-terminus would increase the activity. Analog Ⅱ12 （IC50： 0.08 μmol/L） exhibited similar inhibitory activity to the lead B1, but its synthetic route was simpler than B1. Therefore, Ⅱ12 could be used as a new lead compound for the discovery eco-friendly IGRs.