Discovery of Novel Natural Maltol-Based Derivatives as Potential Succinate Dehydrogenase Inhibitors

To develop novel fungicidal agents, 40 novel maltol-based derivatives were designed, synthesized, and evaluated for antifungal activity. Most compounds exhibited potent in vitro efficacy against phytopathogenic fungi, with A2, A3, A4, A8, A9, A23, A24, and A25 showing strong activity against Rhizoctonia solani. Moreover, compound A2 exerted broad-spectrum antifungal effects against six phytopathogenic fungi. In vivo antifungal activities of compound A24 against Rhizoctonia solani and Botrytis cinerea highlighted its potential in crop protection. Propidium iodide (PI) staining and cellular content release assays indicated that compound A24 disrupted the membrane integrity, thereby inhibiting the mycelial growth and proliferation. Microscopic observations revealed that compound A24 caused irregular morphological alterations in the mycelia and cellular structures. Moreover, compound A24 induced mitochondrial dysfunction, confirmed by mitochondrial membrane potential (MMP) analysis. Succinate dehydrogenase (SDH) enzyme activity assays and molecular docking studies further demonstrated that compound A24 holds considerable promise as a novel SDHI fungicide.