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 A5 displayed satisfactory in vitro fungicidal activity against Fusarium graminearum, Magnaporthe oryzae, Rhizoctonia solani, Colletotrichum gloeosporioides, Botrytis cinerea, Sclerotinia sclerotiorum, Alternaria sp., and Physalospora piricola, with EC50 values of 2.53, 2.84, 1.64, 7.59, 4.67, 5.50, and 2.84 μg mL-1, respectively. Additionally, A5 also showed promising in vivo preventive efficiency against F. graminearum and R. solani at 100 μg mL-1. Preliminary investigation of the fungicidal mechanism demonstrated that the differentially expressed genes and differential metabolites in R. solani treated with A5 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 A5, 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.