Synthesis, Bioactivity Evaluation and Theoretical Study of Nicotinamide Derivatives Containing Diphenyl Ether Fragments as Potential Succinate Dehydrogenase Inhibitors

To obtain nicotinamide fungicides with higher inhibitory activity against Rhizoctonia solani, 24 nicotinamide derivatives were designed and synthesized by introducing the diphenyl ether fragments into the structure of boscalid. Biological assays revealed that the obtained compounds exhibited varying degrees of antifungal activity. Among them, compound 2-chloro-N-(2-(2,4-dichlorophenoxy)phenyl)nicotinamide (7g) exhibited prominent biological activity against R. solani (EC50 = 0.034 mg/L), surpassing the inhibitory effect of boscalid. Experimentally, compound 7g was a promising fungicide with low toxicity that targeted succinate dehydrogenase, as confirmed by the tests of cytotoxicity, inhibition of enzyme activity, mitochondrial membrane potential, and mycelial respiration. This study highlighted the potential of nicotinamide derivatives containing diphenyl ether fragments designed based on theoretical calculations as succinate dehydrogenase inhibitor (SDHI) fungicides.