Synthesis, Structure–Activity Relationship, and Mechanism of a Series of Diarylhydrazide Compounds as Potential Antifungal Agents

• Published in: Journal of agricultural and food chemistry 2023-05, Vol.71 (18), p.6803-6817
• Main Authors: Liu, Ruiyuan, Li, Zhuangzhuang, Liu, Sifan, Zheng, Jinshuo, Zhu, PanPan, Cheng, Bin, Yu, Ruijin, Geng, Huiling
• Format: Article
• Language: English
• Subjects: Agricultural and Environmental Chemistry; Antifungal Agents - chemistry; Ascomycota; Fungicides, Industrial - chemistry; Humans; Structure-Activity Relationship
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.2c08027

A series of simple diarylhydrazide derivatives (45 examples) were well-designed, prepared, and screened for their antifungal activities both in vitro and in vivo. Bioassay results suggested that all designed compounds had significant activity against Alternaria brassicae (EC50 = 0.30–8.35 μg/mL). Among of them, 2c, as the highest activity compound, could effectively inhibit the growth of plant pathogens Pyricularia oryza, Fusarium solani, Alternaria solani, Alternaria brassicae, and Alternaria alternate and was more potent than carbendazim and thiabendazole. 2c showed almost 100% protection at 200 μg/mL in vivo activity against A. solani in tomato. Moreover, 2c did not affect the germination of cowpea seed and the growth of normal human hepatocytes. The preliminary mechanistic exploration documented that 2c could result in the abnormal morphology and irregular structure of the cell membrane, destroy the function of mitochondria, increase the reactive oxygen species, and inhibit the proliferation of hypha cell. The above results manifested that target compound 2c could be a potential fungicidal candidate against phytopathogenic diseases for its excellent fungicidal activities.