杀菌剂氟苯醚酰胺的创制  

Discovery of fungicide flubeneteram

作　　者：曾令强 罗睿童 陈琼[1] 郝格非[1] 朱晓磊[1] 杨光富 ZENG Lingqiang;LUO Ruitong;CHEN Qiong;HAO Gefei;ZHU Xiaolei;YANG Guangfu(Key Laboratory of Pesticide&Chemical Biology,Ministry of Education,College of Chemistry,Central China Normal University,Wuhan 430079,China)

机构地区：[1]华中师范大学化学学院农药与化学生物学教育部重点实验室,武汉430079

出　　处：《农药学学报》2022年第5期895-903,共9页Chinese Journal of Pesticide Science

基　　金：湖北省科技厅重点研发项目(2020BBA052);国家自然科学基金面上项目(21977035,21837001).

摘　　要：琥珀酸脱氢酶(succinate dehydrogenase,SDH)是重要的杀菌剂靶标之一,而很多植物病原菌对靶向SDH的杀菌剂已经产生了较为严重的抗药性,因此新型靶向SDH的杀菌剂设计显得尤为重要。基于药效团连接碎片的虚拟筛选(PFVS)是一种独立于生物物理技术的高通量药物发现方法,采用PFVS方法成功获得了靶向SDH的新型杀菌剂候选化合物—氟苯醚酰胺。本文主要从PFVS原理、先导化合物的发现、取代基的修饰以及杀菌活性研究等方面对氟苯醚酰胺的创制进行系统分析。氟苯醚酰胺创制的案例分析可为农药研究工作者提供新思路和新方法。Succinate dehydrogenase(SDH)is one of the important fungicide targets.However,many plant pathogens showed medium and even high resistance to commercial fungicides targeting upon SDH.So,it is very urgent to design new novel inhibitor for SDH.Pharmacophore-linked fragment virtual screening(PFVS)is a high-throughput drug discovery approach independent of biophysical screening techniques and flubeneteram,a novel fungicide candidate targeting SDH,was successfully obtained by PFVS.Here,the development process of the fungicide flubeneteram was analyzed in detail,including the principle of PFVS,the discovery of lead compounds,the modification of substituents and the fungicidal activity.The discovery process of flubeneteram would provide novel ideas and methods for pesticide researchers.

关 键 词：药效团连接碎片的虚拟筛选 琥珀酸脱氢酶 氟苯醚酰胺 杀菌剂 

分 类 号：TP391[自动化与计算机技术—计算机应用技术] TQ450.1[自动化与计算机技术—计算机科学与技术]