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(1)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 againstRhizoctonia solani. Especially, compounds17(EC50= 6.32 mg/L) and18(EC50= 6.06 mg/L) exhibited good antifungal activities againstR. solaniand were superior to the lead fungicide benodanil (a succinate dehydrogenase inhibitor, SDHI) (EC50= 6.38 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media with the addition of compound17grew abnormally as compared with the negative control with tenuous, wizened, and overlapping colonies, and compounds17(IC50= 52.58 mg/L) and18(IC50= 56.86 mg/L) showed better inhibition abilities against succinate dehydrogenase (SDH) than benodanil (IC50= 62.02 mg/L). Molecular docking revealed that compound17fit 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 compound17and the residue C/Trp-73. These studies suggested that compound17could act as a potential fungicide to be used for further optimization.