An Investigation on Synthesis, Antiphytopathogenic Fungi Activities, and Action Mechanism of TPP-Driven Mitochondria-Targeting Coumoxystrobin Analogues

Coumoxystrobin inhibits the mitochondrial respiratory chain Qo site of Complex III to control apple tree rot, yet it has a narrow fungicidal spectrum and cross-resistance with other methoxyacrylate fungicides. Herein, three classes of triphenylphosphonium (TPP)-conjugated derivatives were designed via a mitochondrial targeting strategy. Screening showed Class I derivatives (linked at the ester site) exhibited superior activity to Class II and III ones (linked via the coumarin unit). Specifically, compound Ia had broad-spectrum efficacy, with EC 50 values of 3.48 μM against S. sclerotiorum, 2.62 μM against B. cinerea and 3.26 μM against R. solani AG-1-IA, as well as excellent in vivo preventive and curative effects on infected tomato fruits and rice leaves. Mechanistically, TPP promoted intracellular accumulation of Ia, which inhibited fungal respiration and ATP production, induced reactive oxygen species burst and mitochondrial damage, thus exerting high fungicidal activity. This study confirms the potential of TPP-mediated mitochondrial targeting in developing novel agricultural fungicides.