Evaluation of Novel Pyridine-Based Compounds Integrating Bioactive Amide and Hydrazide Groups as a Potential Fungicide Agent

A series of novel pyridine-based compounds integrating bioactive amide and hydrazide groups were designed and synthesized through an active group splicing strategy. The fungicidal bioassays indicated that several compounds showed remarkable and broad-spectrum inhibitory activity. Notably, compound <b>A5</b> displayed satisfactory <i>in vitro</i> fungicidal activity against <i>Fusarium graminearum</i>, <i>Magnaporthe oryzae</i>, <i>Rhizoctonia solani</i>, <i>Colletotrichum gloeosporioides</i>, <i>Botrytis cinerea</i>, <i>Sclerotinia sclerotiorum</i>, <i>Alternaria</i> sp., and <i>Physalospora piricola</i>, with EC₅₀ values of 2.53, 2.84, 1.64, 7.59, 4.67, 5.50, and 2.84 μg mL^-1, respectively. Additionally, <b>A5</b> also showed promising <i>in vivo</i> preventive efficiency against <i>F. graminearum</i> and <i>R. solani</i> at 100 μg mL^-1. Preliminary investigation of the fungicidal mechanism demonstrated that the differentially expressed genes and differential metabolites in <i>R. solani</i> treated with <b>A5</b> at 10 μg mL^-1 exhibited notable enrichment in pathways associated with lipid metabolism, potentially linking to the plasma membrane contraction observed by TEM. Furthermore, to assess the environmental compatibility of compound <b>A5</b>, its toxicity to zebrafish, hydrolysis rates in different pH buffers, and effects on the growth of wheat seedlings were evaluated. These findings will provide substantial theoretical guidance for the development of new environmentally friendly fungicides.