Synthesis and Biological Evaluation of Novel Benodanil-Heterocyclic Carboxamide Hybrids as a Potential Succinate Dehydrogenase Inhibitors.

In order to discover new antifungal agents, twenty novel benodanil-heterocyclic carboxamide hybrids were designed, synthesized, and characterized by H NMR and HRMS. In vitro, their antifungal activities against four phytopathogenic fungi were evaluated, as well as some of the target compounds at 50 mg/L demonstrated significant antifungal activities against . Especially, compounds (EC = 6.32 mg/L) and (EC = 6.06 mg/L) exhibited good antifungal activities against and were superior to the lead fungicide benodanil (a succinate dehydrogenase inhibitor, SDHI) (EC = 6.38 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media with the addition of compound grew abnormally as compared with the negative control with tenuous, wizened, and overlapping colonies, and compounds (IC = 52.58 mg/L) and (IC = 56.86 mg/L) showed better inhibition abilities against succinate dehydrogenase (SDH) than benodanil (IC = 62.02 mg/L). Molecular docking revealed that compound fit in the gap composed of subunit B, C, and D of SDH. Furthermore, it was shown that the main interaction, one hydrogen bond interaction, was observed between compound and the residue C/Trp-73. These studies suggested that compound could act as a potential fungicide to be used for further optimization.