Synthesis and antifungal activity evaluation of novel pyridine derivatives as potential succinate dehydrogenase inhibitors

Two series of novel pyridine derivatives (1a−l, 2a−l) were synthesized and characterized by IR, 1H NMR, 13C NMR, and HRMS. The crystal structures of compounds 1 h and 2l were characterized by single crystal X-ray diffraction and crystallized in the monoclinic and orthorhombic system, respectively. The in vitro antifungal activity of synthesized compounds were determined against five plant pathogenic fungi namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum and most of the target compounds revealed significant antifungal activity at 20 mg/L. Of these, the inhibitory rate and the median effect concentrations (EC50) of compounds 1 m, 2i, 2o, and 2p were more close to fluopyram against B. cinerea. Meanwhile, the half inhibitory concentrations (IC50) of compounds 1 m, 2i, 2o, and 2p against succinate dehydrogenase (SDH) and their score in molecular docking were also more close to fluopyram, indicating the stronger antifungal activities of the four compounds were well associated with the affinities of these compounds in interacting with SDH. Therefore, we concluded that compounds 1 m, 2i, 2o, and 2p might be potential succinate dehydrogenase inhibitors (SDHIs), which was been reported for the first time.