Structure
optimization based on natural products has become an
effective way to develop new green fungicides. In this project, thirty-two
novel NPs-derived hydrazide compounds were designed and synthesized
by introducing the bioactive hydrazide substructure into sinapic acid
and mycophenolic acid. The fungicidal bioassays indicated that the
obtained hydrazide compounds showed excellent and selective fungicidal
activity against specific pathogens, especially compounds C8, D7, and D8 with EC50 values
of 0.63, 0.56, and 0.43 μg mL–1 against M. oryzae, respectively. SAR indicated that the introduction
of 4-fluoro, 4-chloro, and 2,4-difluoro groups was conducive to improving
the fungicidal activity, while the extension of the hydrazide bridge
would affect the selectivity for inhibitory activity. Subsequently,
the effects of hydrazide compounds on rice seedling and zebrafish
growth were also investigated. The fungicidal mechanism implied that
treatment with compound B4 would cause significant changes
in metabolites of plasma membrane-related linolenic acid metabolism,
arachidonic acid metabolism, and α-linolenic acid metabolism
pathways, which further led to the wrinkled hyphae and the blurred
plasma membrane and cytoplasm. Finally, the frontier molecular orbitals
and charge distribution were calculated to analyze the differences
in bioactivity from a structural perspective. These results provide
important guidance for the development and practical application of
novel fungicides.