Design, Synthesis, and Evaluation of N'-Phenylisonicotinohydrazides With Broad-Spectrum Antifungal Activity Against Phytopathogenic Fungi.

Developments of novel antifungal agents with unique scaffolds are crucial for sustainable plant protection. In this study, a series of N'-phenylisonicotinohydrazides were designed and synthesized, and their antifungal activity against eight phytopathogenic fungi was evaluated. The results found that most of the target compounds showed excellent antifungal activity with more than 80% inhibition rates against most or all of the tested fungi at 20 µg/mL. Key compounds A1-6 and A1-22 exhibited the best potent antifungal activity, with EC values <1.0 µg/mL against most fungi. Molecular docking revealed the compound A1-1 could well bind to succinate dehydrogenase (SDH) via hydrogen bonding, π-system interactions, and hydrophobic forces. Structure-activity relationships identified para-substitution or halogen atomic substitution as optimal for activity enhancement. These findings establish N'-phenylisonicotinohydrazides, particularly A1-6 and A1-22, as promising candidates for novel fungicide development.