文献类型：期刊文献

英文题名：Discovery of Novel Nicotinamide Derivatives by a Two-Step Strategy of Azo-Incorporating and Bioisosteric Replacement

作者：Ru, Yifan[1];Fu, Wen[1];Guo, Sifan[1];Li, Xiaoyan[2];Zhou, Cong[1];Xu, Zhiping[1];Cheng, Jiagao[1];Li, Zhong[1,3];Shao, Xusheng[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Yantai Inst China Agr Univ, Coll Humanities & Econ Management, Yantai 264670, Shandong, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2024

卷号：72

期号：38

起止页码：20794

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20243817069385);WOS:【SCI-EXPANDED(收录号:WOS:001313750400001)】；

基金：This work was financially supported by the National Natural Science Foundation of China (21877039, 32072441, 32472610, and 32402439), the National Key Research and Development Program of China (2018YFD0200100), the Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-02-E00037), the Tobacco and Health Funding Program (2022539200340111), the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission), and the project of National Key Laboratory of Green Pesticide/Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University (SKL-GPL-KF-202405).

语种：英文

外文关键词：nicotinamide; azo-incorporating; bioisostericreplacement; fungicidal spectrum; SDH

摘要：Azobenzene moieties can serve as active fragments in antimicrobials and exert trans/cis conversions of molecules. Herein, a series of novel nicotinamide derivatives (NTMs) were developed by employing a two-step strategy, including azo-incorporating and bioisosteric replacement. Azo-incorporation can conveniently provide compounds that can be easily optically interconverted between trans/cis isomers, enhancing the structural diversity of azo compounds. It is noteworthy that the replacement of the azo bond with a 1,2,4-oxadiazole motif through further bioisosteric replacement led to the discovery of a novel compound, NTM18, which made a breakthrough in preventing rice sheath blight disease. A control effect value of 94.44% against Rhizoctonia solani could be observed on NTM18, while only 11.11% was determined for boscalid at 200 mgL-1. Further mechanism validations were conducted, and the molecular docking analysis demonstrated that compound NTM18 might have a tight binding with SDH via an extra pi-pi interaction between the oxadiazole ring and residue of D_Y586. This work sets up a typical case for the united applications of azo-incorporating and bioisosteric replacement in fungicide design, posing an innovative approach in structural diversity-based development of pesticides.