Design, synthesis, antifungal activity and mechanism of novel thiourea glycosides based on N-acetyl-glucosamine

To explore the potential of utilizing renewable bioresources as sustainable alternatives to fossil-derived chemicals in green pesticide development, N -acetylglucosamine (NAG), the monomer of chitin, was employed as a starting scaffold for structural design, synthesis, and bioactivity evaluation. An efficient room-temperature synthetic route was developed, successfully yielding a series of novel thiourea glycoside conjugates. In vitro screening identified glycoside 3m as the most potent candidate against Fusarium oxysporum , achieving an inhibition rate of 94.4% at 200 μg/mL. Morphological and ultrastructural analyses via SEM and TEM showed that while glycoside 3m induced notable surface distortions in mycelia, the cell wall and membrane remained intact. Further untargeted metabolomics studies suggested that glycoside 3m primarily suppresses fungal growth by perturbing mitochondrial energy metabolic pathways, including glycolysis and the tricarboxylic acid cycle. Capitalizing on this bioenergetic vulnerability, a synergistic formulation combining glycoside 3m with hydrogen peroxide (H 2 O 2 ) was evaluated. The co-application of 100 μg/mL glycoside 3m with 0.3‰ H 2 O 2 achieved a 100.0% inhibition rate in vitro and a 52.9% protective efficacy in vivo . Overall, this study demonstrates the feasibility of developing high-efficiency fungicides from renewable marine biomass, offering a promising and sustainable approach for the management of agricultural pathogenic fungi.