LAUSR

BACKGROUND Succinate dehydrogenase inhibitor (SDHI) fungicides are an important class of agricultural fungicides with the advantages of high efficiency and a broad bactericidal spectrum. In order to pursue novel SDHIs, a series of N-substituted dithiin tetracarboximide derivatives were designed, synthesized, and characterized by 1 H NMR, 13 C NMR, and HRMS. RESULTS These engineered compounds displayed potent fungicidal activities against phytopathogens, including Sclerotinia sclerotiorum, Botrytis cinerea, and Rhizoctonia solani, comparable to that of the commercial SDHI fungicide boscalid. In particular, compound 18 stood out with prominent activity against S. sclerotiorum with an EC50 value of 1.37 μg/mL. Compound 1 exhibited the most potent antifungal activity against B. cinerea with EC50 values of 5.02 μg/mL. As for R. solani, 12 and 13 exhibited remarkably inhibitory activity with the EC50 value of 4.26 and 5.76 μg/mL, respectively. In the succinate dehydrogenase (SDH) inhibition assay, compound 13 presented significant inhibitory activity with an IC50 value of 15.3 μM, which was approximately equivalent to that of boscalid (14.2 μM). Furthermore, molecular docking studies revealed that compound 13 could anchor in the binding site of SDH. CONCLUSION Taken together, results suggested that the dithiin tetracarboximide scaffold possessed a huge potential to be developed as novel fungicides and succinate dehydrogenase inhibitors.