Development and Biological Evaluation of New Diphenyl Ether Formylhydrazide Compounds as Potent Inhibitors of Succinate Dehydrogenase.

Autor: He B; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Chen W; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Fu L; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Hu M; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Xiong Z; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Luo X; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Hu Y; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Mu Y; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., He X; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Yan W; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China., Ye Y; State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.; Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China.
Jazyk: angličtina
Zdroj: Journal of agricultural and food chemistry [J Agric Food Chem] 2024 Nov 27; Vol. 72 (47), pp. 26133-26141. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1021/acs.jafc.4c07019
Abstrakt: Succinate dehydrogenase (SDH), also recognized as succinate ubiquinone oxidoreductase (SQR), is considered one of the most promising targets for fungicide development, garnering significant international interest. We have focused on the development of highly effective, broad-spectrum-targeted SDH inhibitors. Using an active scaffold combining strategy, we designed and synthesized a series of novel diphenyl ether formylhydrazine derivatives, and most compounds have demonstrated broad-spectrum antifungal activity. Notably, compound M8 exhibited antifungal activity of more than 93% against four tested pathogen types at a concentration of 10 μg/mL, with an EC 50 value below 0.3 μg/mL for each pathogen, outperforming boscalid. Additionally, compound M8 exhibited a control efficacy of 83% against Sclerotinia sclerotiorum on rapeseed leaves at a concentration of 200 μg/mL and demonstrated an 87% efficacy in controlling Fusarium graminearum on wheat ears when applied at 400 μg/mL. Structure-activity relationship research suggested that para-substituted benzene rings are more effective, offering stronger and more extensive antifungal potency. Further investigation, including enzyme inhibition assays, mycelial morphology observations, and molecular docking studies, suggests that the antifungal potency of M8 is due to the inhibition of its SDH activity. Therefore, our research positions compound M8 as a highly promising lead compound with broad-spectrum antifungal properties, potentially introducing a new class of fungicide.
Databáze: MEDLINE