Novel Formononetin Derivatives Containing Piperidine and Isoxazole Moieties: Discovery and Preliminary Mechanistic Exploration of Potential Phytophthora capsici Inhibitors

Abstract Twenty-two formononetin derivatives containing piperidine and isoxazole moieties were designed and synthesized, and the antifungal/anti-oomycete activities of the target compounds were assessed in vitro against ten plant pathogens. Among them, Y9 exhibited the most potent activity against Phytophthora capsici, with an EC50 of 6.3 μg/mL, outperforming the commercial fungicide azoxystrobin (Az, 88.5 μg/mL). In curative assays on detached chili leaves and eggplant fruits, Y9 applied at 200 μg/mL achieved impressive efficacy rates of 76.4% and 45.2%, respectively, surpassing those of Az (69.2% and 17.5%) at the same concentration. Mechanistically, Y9 was found to induce membrane damage, mitochondrial dysfunction, ROS accumulation, and MMP dissipation in P. capsici hyphae. These cellular responses may contribute to the inhibition of hyphal growth and disruption of cellular homeostasis, suggesting that Y9 represents a promising anti-oomycete candidate for further development.