Liu Xuelian, Yang Dongyan, Yin Fahong, Li Jia-Qi, Xiao Yumei, Fu Bin, Qin Zhaohai
College of Sciences, China Agricultural University Beijing 100193 China
RSC Adv. 2020 Nov 24;10(70):42804-42809. doi: 10.1039/d0ra06263d. eCollection 2020 Nov 23.
Based on the "plug-in molecular" method, a series of novel strobilurin derivatives with aryloxypyridinyl-1-ethanone oxime side chains were designed, synthesized, and screened. The biological activity experiment showed that they had an excellent fungicidal effect on plant pathogens, especially . Compounds 5-01 and 5-09 had significant fungicidal activity and broad fungicidal spectrum. The structure-activity relationship indicates that the configuration, increasing the number of pharmacophores, substitution of the 2 position of the pyridine ring, and the introduction of chlorine atom on the benzene ring were not conducive to the fungicidal activity of such compounds. The model of 3D-QSAR indicated the introduction of large electropositive groups at the 4 position of the benzene ring and the introduction of small electronegative groups at the 2 position of the benzene ring were beneficial to the fungicidal activity, and compounds 6 were designed. Compared with azoxystrobin, compound 6-02 had a more effective fungicidal effect against (Lib.) de Bary. Cytotoxicity test and transmission electron microscopy showed that the modification of strobilurins fungicide by the "plug-in molecular" method would not affect its toxicity and mechanism. The "plug-in molecular" method is an efficient method for screening highly active compounds, which has important guiding significance for creating new pesticide molecules.
基于“插入分子”方法，设计、合成并筛选了一系列具有芳氧基吡啶基-1-乙酮肟侧链的新型甲氧基丙烯酸酯类衍生物。生物活性实验表明，它们对植物病原菌具有优异的杀菌效果，尤其是化合物5-01和5-09具有显著的杀菌活性和广谱杀菌谱。构效关系表明，构型、药效基团数量的增加、吡啶环2位的取代以及苯环上氯原子的引入均不利于此类化合物的杀菌活性。三维定量构效关系模型表明，在苯环4位引入大的正电基团以及在苯环2位引入小的负电基团有利于杀菌活性，并设计了化合物6。与嘧菌酯相比，化合物6-02对（Lib.）德巴利具有更有效的杀菌效果。细胞毒性测试和透射电子显微镜表明，通过“插入分子”方法对甲氧基丙烯酸酯类杀菌剂进行修饰不会影响其毒性和作用机制。“插入分子”方法是筛选高活性化合物的有效方法，对创制新型农药分子具有重要指导意义。
