Xuewen Hua1, Wenrui Liu1, Yanyan Su1, Xinghai Liu2, Jingbo Liu3, Nannan Liu1, Guiqing Wang1, Xueqin Jiao1, Xiaoyi Fan1, Chenmeng Xue1, Yi Liu1, Ming Liu4. 1. College of Agriculture, Liaocheng University, Liaocheng, P. R. China. 2. College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou, P. R. China. 3. College of Horticulture and Landscape Architecture, Tianjin Agricultural University, Tianjin, P. R. China. 4. College of Pharmacy, Binzhou Medical University, Yantai, P. R. China.
Abstract
BACKGROUND: Succinate dehydrogenase (SDH) has been identified as one of the most significant targets for fungicide discovery. To date, 23 commercial SDH inhibitor (SDHI) fungicides have been approved for plant protection since the first launch of carboxin in 1966, and extensively applied to combat destructive plant fungi. RESULTS: In this project, 20 novel pyridine sulfide derivatives containing SDH-based heterocyclic amide fungicide were designed, synthesized, and characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR and high-resolution mass spectrometry (HRMS). In vitro fungicidal activity experiment, the target compound I-1 displayed excellent inhibitory rates against the common agricultural pathogens with half maximal effective concentration (EC50 ) values of 5.2 to 39.8 μg mL-1 . The in vivo fungicidal activities demonstrated that the compound I-1 could effectively prevent Botrytis cinerea from infecting tomato and cucumber leaves with the preventative rates of 67% and 50%. The mitochondrial membrane potential detection, SDH enzyme assay and the molecular docking simulation revealed that the mechanism of action of the compound I-1 and the relevant interactions with the target enzyme may be similar to those of the control fluopyram. CONCLUSION: The biological activity screening and validation of mechanism of action indicated that the compound I-1 could be identified as a potential SDH inhibitor for further study.
BACKGROUND:Succinate dehydrogenase (SDH) has been identified as one of the most significant targets for fungicide discovery. To date, 23 commercial SDH inhibitor (SDHI) fungicides have been approved for plant protection since the first launch of carboxin in 1966, and extensively applied to combat destructive plant fungi. RESULTS: In this project, 20 novel pyridine sulfide derivatives containing SDH-based heterocyclic amide fungicide were designed, synthesized, and characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR and high-resolution mass spectrometry (HRMS). In vitro fungicidal activity experiment, the target compound I-1 displayed excellent inhibitory rates against the common agricultural pathogens with half maximal effective concentration (EC50 ) values of 5.2 to 39.8 μg mL-1 . The in vivo fungicidal activities demonstrated that the compound I-1 could effectively prevent Botrytis cinerea from infecting tomato and cucumber leaves with the preventative rates of 67% and 50%. The mitochondrial membrane potential detection, SDH enzyme assay and the molecular docking simulation revealed that the mechanism of action of the compound I-1 and the relevant interactions with the target enzyme may be similar to those of the control fluopyram. CONCLUSION: The biological activity screening and validation of mechanism of action indicated that the compound I-1 could be identified as a potential SDH inhibitor for further study.