文献类型：期刊文献

英文题名：Synthesis and Biological Activity of Novel Antifungal Leads: 3,5-Dichlorobenzyl Ester Derivatives

作者：Du, Shaoqing[1];Yuan, Qinglong[1];Hu, Xueping[2];Fu, Wen[1];Xu, Qi[1];Wei, Ziyi[1];Xu, Jiazheng[1];Shao, Xusheng[1];Qian, Xuhong[1,3]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou Inst Innovat Med, Hangzhou 310058, Zhejiang, Peoples R China;[3]East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China

年份：2021

卷号：69

期号：51

起止页码：15521

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20220111411460);WOS:【SCI-EXPANDED(收录号:WOS:000734500200001)】；

基金：This work was financially supported by Key Project of the Shanghai Science and Technology Committee (No.18DZ1112703) and the National Natural Science Foundation of China (No.31830076, No.21977030, and No. 21907084).

语种：英文

外文关键词：succinate dehydrogenase inhibitors; fungicidal activity; molecular dynamic simulations; 3,5-dichlorobenzyl ester

摘要：Succinate dehydrogenase (SDH) is one of the most important molecular targets for the development of new fungicides. Carboxamide fungicides are a class of SDH inhibitors widely used to inhibit highly destructive plant pathogens. Although cases of resistance have been found in fungal pathogens due to the unrestricted use in recent years, there is still demand for new compounds with improved fungicidal activity. Therefore, a series of ester compounds were designed to investigate potential novel antifungal molecules. First, the antifungal activity of different benzyl alcohol compounds (A1-A21) was tested, and a highly active fragment (3,5-dichlorobenzyl alcohol) was found. Subsequently, various compounds were synthesized by esterification between different acids and 3,5-dichlorobenzyl alcohol, among which compound 5 exhibited remarkable antifungal activity against Botrytis cinerea and Rhizoctonia solani with EC50 values of 6.60 and 1.61 mg/L, respectively, which were comparable to those of commercial fungicide boscalid (EC50 = 1.24 and 1.01 mg/L). In vivo testing further demonstrated that compound 5 was effective in suppressing B. cinerea (200 mg/L, 50.9%). Moreover, SDH inhibition assays, fluorescence quenching analysis, and determination of mitochondrial membrane potential revealed that compound 5 has similar effects to boscalid. Furthermore, the fungicidal activity of target compounds can be maintained by modifying the amide bond to an ester bond. These results will provide basis for the development of novel fungicides.