Novel pyran derivatives as potential succinate dehydrogenase inhibitors: design, synthesis, crystal structure, biological activity, and molecular modeling

Twenty-six novel pyran derivatives (1a−m, 2a−m) were designed, synthesized, and characterized by IR, 1H NMR, 13C NMR, and HRMS. The crystal structures of compound 2f was characterized by single crystal X-ray diffraction and crystallized in the monoclinic system with space group P21/c. The in vitro antifungal activities of these synthesized compounds were evaluated against five plant pathogenic fungi namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Penicillium digitatum, and Sclerotinia sclerotiorum and most of the synthesized compounds displayed good to excellent antifungal activities at 20 µg/mL. Of these, the inhibitory rates and the median effect concentrations (EC50) of compound 2e against R. Solani, compounds 1b, 1e, 2a, 2b, and 2c against S. sclerotiorum, and compounds 1a and 2i against H. maydis were better than fluopyram against the relative fungi. Besides, the half inhibitory concentrations (IC50) of compounds 1b, 1e, 2a, 2b, and 2c against succinate dehydrogenase (SDH) and their scores in molecular docking were both lower than that of fluopyram, indicating that these synthesized compounds possessed stronger antifungal activities and affinities than fluopyram. Therefore, we concluded that compounds 1b, 1e, 2a, 2b, and 2c might serve as potential succinate dehydrogenase inhibitors (SDHIs), which was been reported for the first time.