Discovery and Preliminary Mechanistic Investigation of 5-Aminoquinoline Hydrazone Derivatives as Antifungal Leads against Sclerotinia sclerotiorum

Abstract

Sclerotinia sclerotiorum is a destructive necrotrophic pathogen that causes severe yield losses in economically important crops. In this study, a series of 5-aminoquinoline-based hydrazone derivatives were designed and synthesized, and their antifungal activity was evaluated. Compound A16 exhibited superior activity against S. sclerotiorum (EC50 = 2.42 μg/mL) and Phomopsis sp. (EC50 = 5.32 μg/mL), outperforming the commercial fungicide oxine-copper. In-vivo tests demonstrated that A16 possessed excellent curative (94.5%) and protective (72.9%) efficacies. Preliminary mechanistic studies showed that A16 inhibited succinate dehydrogenase activity, perturbed membrane-associated physiological processes, and promoted the accumulation of intracellular reactive oxygen species accumulation, indicating substantial disruption of fungal energy and redox homeostasis. Moreover, A16 exhibited relatively low toxicity toward zebrafish under the tested conditions. These results suggest that A16 is a promising lead compound worthy of further optimization for the development of fungicidal agents for the management of Sclerotinia diseases.