Design, Synthesis, and Antifungal Activities of Hymexazol Glycosides Based on a Biomimetic Strategy

Abstract

Hymexazol (HYM) is irreplaceable for treating soil-borne diseases due to its high efficiency and low cost, as a broad-spectrum fungicide. However, when HYM is absorbed by plants, it is rapidly converted into two glycoside metabolites, and the antifungal activities of these glycosides are inferior to that of HYM. Therefore, in this study, to maintain strong antifungal activity in vitro and in vivo, HYM was glycosylated with amino sugars that have diverse biological activities to simulate plant glycosylation. The antifungal experiment proved that glycoside 15 has the highest antifungal activity, and N-acetyl glucosamine and HYM had obvious synergistic effects. According to the structure–activity relationship studies, glycoside 15 had greater numbers of active electron-rich regions and front-line orbital electrons due to the introduction of N-acetyl glucosamine. Moreover, glycoside 15 can significantly promote plant growth and induce an increase in plant defense enzyme activity. Additionally, compared to HYM, the results of electron microscopy and proteomics revealed that glycoside 15 has a unique antifungal mechanism. The promising antifungal activity and interactions with plants mean that glycoside 15 is a potential green fungicide candidate. Furthermore, this research conducted an interesting exploration of the agricultural applications of amino sugars.

Various Biomimetics as Antifungals

“…To inhibit the enzymatic activity of fungi, synthetic substrates, playing role of mimetics, or specific inhibitors can be used to reduce the metabolic activity of fungi or to carry out their catalytic or physiological functions, reducing the biosynthesis of a number of metabolites and preventing their growth (Table 4) [15,[91][92][93][94][95][96][97][98]. Biomimetic substrates should, on the one hand, inhibit the widest possible range of fungal enzymes, and on the other hand, not be inhibitors for enzymes of plant and animal origins.…”

“…Modification of HYM by amino sugars significantly stimulates plant growth, but causes morphological changes in the mycelium Alternaria alternata: plasma membranes are separated from cell walls, cytoplasm becomes vacuolized, and mitochondria, lysosomes and other organelles decrease in size in cells, the mechanical strength of cell walls is significantly reduced. Glycosylated HB suppresses the activity of chitin synthase G involved in chitin biosynthesis, which leads to these changes in cells and limits their growth [15].…”

“…In addition to AFPs, the synthesis of a number of other compounds and materials forming various surfaces imitating natural analogues that can be attributed to biomimetics is also interesting from scientific and practical point of view. The antifungal effect of these compounds and materials is not limited to the destruction of the cell wall and membranes of fungi, but affects their various metabolically important pathways, growth and spore formation [15][16][17]. Of great interest is the possible synergistic effect among such biomimetics with antifungal drugs, which allows to reduce the doses of individual substances used [18,19].…”

A dual pesticide–fertilizer silicon-base nanocomposite to synergistically control fungal disease and provide nutrition

“…28 Hymexazol (Hym) is a systemic fungicide and soil disinfectant, as well as a plant growth regulator, that can not only effectively inhibit the growth of pathogenic fungi mycelium but also promote the development of crop roots. 29,30 In this study, a pH-responsive degradable dual pesticide bimetallic fertilizer nanoparticle (Pro@Cu-MSNs-ZnO/Hym) was constructed. Copper ions (Cu 2+ ) were doped into the frame structure of mesoporous silica, and ZnO was employed as a nanocap by amide bond linkage to block pesticide release.…”

“…28 Hymexazol (Hym) is a systemic fungicide and soil disinfectant, as well as a plant growth regulator, that can not only effectively inhibit the growth of pathogenic fungi mycelium but also promote the development of crop roots. 29,30…”