Discovery of Novel Pyrazol-5-yl-benzamide Derivatives Containing a Thiocyanato Group as Broad-Spectrum Fungicidal Candidates.

In an effort to promote the development of new fungicides, a series of 48 novel -(1-methyl-4-thiocyanato-1-pyrazol-5-yl)-benzamide derivatives - and - were designed and synthesized by incorporating a thiocyanato group into the pyrazole ring, and their fungicidal activities were evaluated against , , , , and . In the antifungal/antioomycete assay, many of the target compounds exhibited good broad-spectrum fungicidal activities. Among them, compound displayed the best antifungal activity against with an EC value of 0.37 mg/L, which was significantly higher than that of the positive controls (13.3 mg/L) and (10.3 mg/L). Meanwhile, compound exhibited the best antioomycete activity against with an EC value of 0.41 mg/L, which was higher than that of (29.2 mg/L) but lower than that of (0.13 mg/L). Notably, compound displayed broad-spectrum inhibitory activities against , , , , and with respective EC values of 0.71, 1.44, 1.78, 0.87, and 1.61 mg/L. The experiments revealed that compounds and presented excellent protective and curative efficacies against , similar to that of the positive control . Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses showed that compound could change the mycelial morphology and severely damage the ultrastructure of . The results of the SDH enzymatic inhibition experiments indicated that compounds and could effectively inhibit the activity of SDH (SDH). Furthermore, molecular docking analysis demonstrated significant hydrogen bonds and Pi-S bonding between the target compounds and the key amino acid residues of SDH, which could explain the probable mechanism of action. Collectively, these studies provide a valuable approach to expanding the fungicidal spectrum of pyrazol-5-yl-benzamide derivatives.