Coumarin Hydrazone Derivatives as Potent Succinate Dehydrogenase Inhibitors and Effective Antifungal Agents against Rhizoctonia solani.

Succinate dehydrogenase inhibitors (SDHIs) are widely used worldwide for their broad-spectrum antifungal activity. Structural optimization of natural products offers a viable route to novel SDHI skeletons. Herein, a series of coumarin hydrazone derivatives were designed and synthesized by a scaffold splicing strategy. Compound 3p showed 100% antifungal activity against Rhizoctonia solani at 50 μg/mL, with an EC50 of 1.16 μg/mL. On rice leaves, 3p achieved 98.4% preventive efficacy against R. solani, outperforming Boscalid (69.6%) at the same concentration. Furthermore, it caused hyphal distortion and mitochondrial damage, similar to boscalid. Enzymatic assays confirmed 3p as an SDHI with an IC50 of 8.69 μM, and molecular docking indicated stable binding within the SDH active site. ATP analysis revealed intracellular levels were reduced to 72% in 3p-treated mycelia compared to controls. Therefore, compound 3p is a promising leader for developing novel SDH inhibitors.