Design, Synthesis, and Biological Evaluation of Novel Pyrazol-5-yl-benzamide Derivatives Containing Oxazole Group as Potential Succinate Dehydrogenase Inhibitors.

A series of pyrazol-5-yl-benzamide derivatives containing the oxazole group were designed and synthesized as potential SDH inhibitors. According to the results of the bioassays, most target compounds displayed moderate-to-excellent antifungal activities against , , , and . Among them, compounds , , and exhibited more excellently inhibitory activities against than (EC = 0.96 mg/L), with EC values of 0.69, 0.26, and 0.95 mg/L, respectively. experiments on rape leaves and cucumber leaves showed that compounds and exhibited considerable protective effects against than . SEM analysis indicated that compounds and significantly destroyed the typical structure and morphology of hyphae. In the respiratory inhibition effect assays, compounds (28.0%) and (33.9%) exhibited a strong inhibitory effect on the respiration rate of mycelia, which was close to (30.6%). The results of molecular docking indicated that compounds and could form strong interactions with the key residues TRP O:173, ARG P:43, TYR Q:58, and MET P:43 of the SDH. Furthermore, the antifungal mechanism of these derivatives was demonstrated by the SDH enzymatic inhibition assay. These results demonstrate that compounds and can be developed into novel SDH inhibitors for crop protection.