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

Abstract

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 in vitro antifungal activities against Valsa mali, Sclerotinia scleotiorum, Alternaria alternata, and Botrytis cinerea. Among them, compounds C13, C14, and C16 exhibited more excellently inhibitory activities against S. sclerotiorum than boscalid (EC50 = 0.96 mg/L), with EC50 values of 0.69, 0.26, and 0.95 mg/L, respectively. In vivo experiments on rape leaves and cucumber leaves showed that compounds C13 and C14 exhibited considerable protective effects against S. sclerotiorum than boscalid. SEM analysis indicated that compounds C13 and C14 significantly destroyed the typical structure and morphology of S. scleotiorum hyphae. In the respiratory inhibition effect assays, compounds C13 (28.0%) and C14 (33.9%) exhibited a strong inhibitory effect on the respiration rate of S. sclerotiorum mycelia, which was close to boscalid (30.6%). The results of molecular docking indicated that compounds C13 and C14 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 C13 and C14 can be developed into novel SDH inhibitors for crop protection.

Design, Synthesis, and Antifungal Activities of Novel Pyrazole-4-carboxamide Derivatives Containing an Ether Group as Potential Succinate Dehydrogenase Inhibitors

“…The detailed method of SEM for this assay was performed according to the literature. , In brief, the mycelia dishes (5 mm in diameter) were inoculated on PDA medium plates containing no ingredient (negative control) and compounds 7d and 12b (concentration = 1 μg/mL) cultured at 25 °C for 2 days. The effect of compounds 7d and 12b on the mycelial morphology of R.…”

Design, Synthesis, and Antifungal Activities of Novel Carboxamides Derivatives Bearing a Chalcone Scaffold as Potential SDHIs

“…The SEM method was used in this study, based on relevant literature. [37][38][39] Mycelia dishes with a diameter of 5 mm were inoculated on PDA medium plates and cultured at 25 °C for 2 days with 5 k, Boscalid (concentration = 1 μg/mL) and negative control. The effect of 5 k and Boscalid on the mycelial morphology of R. solani was observed and studied using SEM.…”

Discovery of Pyrazole-5-yl-amide Derivatives Containing Cinnamamide Structural Fragments as Potential Succinate Dehydrogenase Inhibitors

“…In our previous work, our group designed and synthesized a series of novel pyrazol-5-yl-benzamide derivatives containing the oxazole group as SDH inhibitors. The biological activity test results showed that some compounds exhibited excellent antifungal activities.…”