Potential Succinate Dehydrogenase Inhibitors Bearing a Novel Pyrazole-4-sulfonohydrazide Scaffold: Molecular Design, Antifungal Evaluation, and Action Mechanism

作者：Jianqi Chai, Yudong Mei, Lang Tai, Xiaobin Wang, Min Chen, Xiangyi Kong, Ai‐Min Lu, Guohua Li, Chun-Long Yang · 发表于：Journal of Agricultural and Food Chemistry · 年份：2023 · DOI：10.1021/acs.jafc.3c00126 · 被引用次数：41 · 研究领域：Fungal Plant Pathogen Control、Plant Disease Resistance and Genetics、Plant-Microbe Interactions and Immunity

Aiming to develop novel antifungal agents with a distinctive molecular scaffold targeting succinate dehydrogenase (SDH), 24 N ′-phenyl-1 H -pyrazole-4-sulfonohydrazide derivatives were first devised, synthesized, and verified by 1 H NMR, 13 C NMR, high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction analysis. The bioassays revealed that the target compounds possessed highly efficient and broad-spectrum antifungal activities against four tested plant pathogenic fungi Rhizoctonia solani ( R. solani ), Botrytis cinerea, Fusarium graminearum, and Alternaria sonali . Strikingly, compound B6 was assessed as the selective inhibitor against R. solani, with an in vitro EC 50 value (0.23 μg/mL) that was similar to that of thifluzamide (0.20 μg/mL). The in vivo preventative effect of compound B6 (75.76%) at 200 μg/mL against R. solani was roughly comparable to thifluzamide (84.31%) under the same conditions. The exploration of morphological observations indicated that compound B6 could strongly damage the mycelium morphology, obviously increase the permeability of the cell membrane, and dramatically increase the number of mitochondria. Compound B6 also significantly inhibited SDH enzyme activity with an IC 50 value of 0.28 μg/mL, and its fluorescence quenching dynamic curves were similar to that of thifluzamide. Molecular docking and molecular dynamics simulations demonstrated that compound B6 could strongly interact with similar residues around the SDH active ...