A new library of pyridine carboxamides for the control of peach brown rot: synthesis, antifungal activity, and preliminary mode of action.

Peach (Prunus persica L.) is an economically important fruit crop, yet its yield and quality are severely threatened by brown rot, primarily caused by Monilia fructigena. To address this challenge, a series of novel pyridine carboxamides were designed, synthesized, and evaluated for their antifungal properties. In vitro assays revealed that several compounds, notably II-6, II-9, II-13, II-16, III-4, III-12, and IV-4, exhibited potent antifungal activity against M. fructigena, with EC50 values ranging from 11.5 to 16.1 µg/mL, significantly surpassing the commercial fungicide azoxystrobin (EC50 = 36.9 µg/mL). Importantly, in vivo experiments on peach fruits demonstrated that II-13 displayed exceptional protective and curative efficacy (78.9% and 46.3%, respectively) at 100 µg/mL, markedly outperforming chlorothalonil (47.3% and 35.6%). Mechanistic studies elucidated that II-13 disrupts cellular integrity, as observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showing severe mycelial shrinkage and organelle degradation. Furthermore, physiological analyses indicated that II-13 triggers mitochondrial dysfunction and oxidative stress, characterized by the dissipation of mitochondrial membrane potential (MMP) and excessive accumulation of reactive oxygen species (ROS). These disruptions ultimately lead to irreversible leakage of intracellular macromolecules. Collectively, these findings validate II-13 as a promising lead structure for the development of novel fungicides to combat peach brown rot.