Discovery of Aryloxy-, Arylthio-, and Arylamino-Containing Acethydrazides as Fungicidal Agents

Abstract

The development of new green fungicides is an effective way to solve the resistance of agricultural pathogens and plays an important role in promoting high-quality and sustainable development of modern agriculture. In this project, a series of aryloxy-, arylthio-, and arylamino-containing acethydrazide derivatives were designed, synthesized, and characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectrometry (HRMS). The fungicidal bioassays indicated that some compounds showed excellent and broad-spectrum fungicidal activity, and the structure−activity relationship was discussed. The in vivo fungicidal activity demonstrated that compounds C4 and D8 exhibited good preventative effects against Fusarium graminearum infecting wheat leaves, of which the preventative activity of compound D8 was almost equal to that of the positive agents. Transmission electron microscopy (TEM) observation revealed that the plasma membrane in the C4-treated F. graminearum hyphal cells was severely contracted and separated with the cell wall, coupling with the visible lysosomes and the disappeared cytoplasm and organelles, which may be the reasons for the shriveled and even ruptured hyphae observed by scanning electron microscopy (SEM). Subsequently, transcriptomics and metabolomics were performed to further elucidate the fungicidal mechanism. The regulatory networks of differential genes and metabolites in plasma membrane-related sphingolipid metabolism, linoleic acid metabolism, α-linoleic acid metabolism, and arachidonic acid metabolism were constructed and elaborated. Additionally, preliminary investigation of seeding growth suggested that compounds C4 and D8 may have different degrees of influence on the growth indicators of wheat seedlings; however, this effect may be negligible as the plant grows.

Natural Alkaloid Waltherione F-Derived Hydrazide Compounds Evaluated in an Agricultural Fungicidal Field

“…The investigation of wheat seedling growth treated with the hydrazide compounds was achieved according to our previous work . First, 150 full-grain wheat seeds were prepared, sterilized with 75% alcohol, washed with distilled water, and placed uniformly in five Petri dishes with two filter papers in advance to culture at 25 °C for 7 days.…”

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field

“…Hua’s group , synthesized a series of aryloxy-, arylthio-, and arylamino-containing acethydrazide derivatives 4 (Figure ). The fungicidal bioassays indicated that some compounds showed excellent and broad-spectrum inhibitory activity, of which compounds 4a (X = O, R 1 = 2-F, 4-F) and 4b (X = NH, R 1 = 2-F, 4-F) exhibited inhibitory effects against P. grisea superior to other compounds, with EC 50 values of 0.59 and 0.86 μg/mL.…”

“…Additionally, compounds 85 , 88 , and 89 were also constructed with laccase inhibitors coumarin hydrazone and PMDD-5Y as lead structures and thus proved to be laccase inhibitors as well. However, authors Chen and Fang pointed out, respectively, that the monohydrazide compounds 2f and 4c significantly affected the normal function of plasma membranes, which was different from the fungicidal mechanisms mentioned above. As we know, the plasma membrane is composed of phospholipid bilayers, including glycerophospholipids, sphingolipids, and sterols. − Subsequently, with the help of transcriptomics and metabolomics, author Fang found that the fungicidal mechanism of hydrazide compound 4c was involved in some specific differential genes and differential metabolites in the plasma membrane-associated linoleic acid metabolism, arachidonic acid metabolism, α-linoleic acid metabolism, and sphingolipid metabolism pathways.…”

“…Summary of the fungicidal mechanisms of the reported hydrazide derivatives. Photographs reprinted with permission from ref . Copyright 2022 American Chemical Society.…”

“…In addition, Fang et al 27 also indicated that acethydrazide compound 4c could cause severe contraction of the plasma membrane and separation from the cell wall. Transcriptomics and metabolomics analysis further revealed that compound 4c would affect the plasma membrane-associated linoleic acid metabolism, arachidonic acid metabolism, α-linoleic acid metabolism, and sphingolipid metabolism pathways, thereby influencing the related genes and metabolites.…”