Synthesis, bioactivity evaluation and theoretical study of nicotinamide derivatives containing diphenyl ether fragments as potential succinate dehydrogenase inhibitors.

• Introduce the diphenyl ether fragments into the structure of boscalid, design and synthesize 24 nicotinamide derivatives. • Several highly promising antifungal compounds have been discovered in the synthesized title compounds. • Theoretical calculation reveals the structural characteristics of biphenyl, diphenylamine and diphenyl ether fragments, and offers guidance for further optimization and design of compounds with higher antifungal activity. • Biological evaluation indicates that the title compound 7g is expected to become a candidate for SDHIs with high efficiency and low toxicity. 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 (EC 50 = 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. [Display omitted] [ABSTRACT FROM AUTHOR]