Agrochemical Evaluation of Natural l -Alanine-Derived Amide–Hydrazide Hybrids as Novel Fungicidal Agents in Ensuring Food Security

Food security is under serious threat from plant pathogenic fungi as traditional fungicides face growing challenges due to pathogen resistance and environmental concerns. In this project, 24 novel hydrazide-based target compounds were designed and synthesized, among which compound A5 was discovered to have excellent and broad-spectrum fungicidal activity. Fungicidal mechanism investigations indicated that compound A5 likely interfered with the function of biofilms by modulating the ergosterol biosynthesis pathway. Toxicity evaluation revealed that compound A5 exhibited low toxicity toward zebrafish and little effect on wheat seedling growth, highlighting its eco-compatibility. Notably, the introduction of a methyl group on the hydrazide bridge can significantly reduce the toxicity of compound A5 to zebrafish and improve its stability in an alkaline environment. These findings provide valuable insights for the development of next-generation environmentally benign fungicides with novel modes of action, offering both theoretical guidance and practical support for achieving sustainable crop protection.