Identification of Syringic Hydrazide Derivatives as Promising Succinate Dehydrogenase Inhibitors with Superior Antifungal and Anti-Oomycete Efficacy for Ensuring Food Safety

Abstract Fungal diseases remain a major constraint on global crop production, driving the search for fungicides with broader efficacy and improved selectivity. Confronting the dual challenges of structural rigidity and declining antifungal performance in conventional succinate dehydrogenase inhibitors (SDHIs), this study developed novel syringic acid derivatives. Notably, W11 exhibited remarkable broad-spectrum potency against eight phytopathogenic fungi and two oomycete species, with EC50 values of 0.679, 0.424, and 0.384 μg/mL against Gibberella zeae, Alternaria solani, and Colletotrichum fructicola, respectively. This activity significantly surpassed that of the commercial fungicide boscalid (EC50 >25.0, 0.826, and >25.0 μg/mL). Interestingly, W11 exhibited excellent succinate dehydrogenase inhibitory activity, causing a marked increase in intracellular reactive oxygen species (ROS), severe mitochondrial damage, and ultimately cell death. Overall, this work presents a structure-driven strategy that expands the antifungal spectrum of SDHIs and offers a promising scaffold for developing eco-friendly agrochemicals to address both limited antifungal activity and emerging oomycete challenges in sustainable agriculture.