文献类型：期刊文献

中文题名：新型靶向烟酰胺酶PROTACs的设计、合成及其生物活性

英文题名：Design,synthesis and bioactivity of novel nicotinamidase PROTACs

作者：邓捷[1];张振国[1];盛祝波[1];邵旭升[1]

机构：[1]华东理工大学药学院上海市化学生物学重点实验室,上海200237

年份：2025

卷号：64

期号：6

起止页码：399

中文期刊名：农药

外文期刊名：Agrochemicals

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金(32472610,32072441);国家重点研发计划(2018YFD0200100)。

语种：中文

中文关键词：蛋白降解靶向嵌合体;烟酰胺酶;氟啶虫酰胺;杀虫剂

外文关键词：proteolysis-targeting chimeras;nicotinamidase;flonicamid;insecticide

摘要：[目的]探究新型靶向烟酰胺酶PROTACs在农业害虫防治中的应用。[方法]以6-氯-4-三氟甲基烟酸为起始原料,通过7个反应步骤合成5个靶向烟酰胺酶的小分子蛋白降解靶向嵌合体,通过1H NMR和高分辨质谱对其结构进行验证。[结果]杀虫活性数据显示,化合物A1-A5在100 mg/L时对苜蓿蚜成虫和褐飞虱1龄若虫表现出一定的杀虫活性,其中化合物A1和A4对苜蓿蚜成虫的杀虫活性最好,致死率分别为95.63%和91.85%;对褐飞虱1龄若虫的致死率分别为82.24%和73.56%;在500 mg/L时,化合物A1对草地贪夜蛾初孵幼虫的致死率为88.65%,对虫卵孵化的抑制率为59.24%。蛋白免疫印迹结果表明,Sf9细胞中未发现烟酰胺酶(NAAM)降解现象。
[Aims]To explore the application of novel targeted nicotinamidase PROTACs in agricultural pest control.[Methods]Using 6-chloro-4-trifluoromethylnicotinic acid as starting material,five small molecules of PROTACs targeting nicotinamidase were systematically synthesized by seven reaction steps.Their structures were verified by'H NMR and HRMS.[Results]The insecticidal activity data indicated that compounds A1-A5 displayed certain insecticidal activity against Aphis craccivora and 1st instar Nilaparvata lugens at 100 mg/L.Compounds Al and A4 displayed the best activity against A.craccivora with mortality rate of 95.63%and 91.85%,and showed 82.24%and 73.56%activity against Ist instar N.lugens,respectively.At 500 mg/L,compound A1 achieved a mortality rate of 88.65%against the 1st instar Spodoptera frugiperda,and moderated inhibition of 59.24%to eggs.Western blot result demonstrated that none of the Sf9 cells showed degradation of nicotinamidase(NAAM).