Luo Bo, Wu Yanbing, Cao Mengfan, Liu Chendan, Xiong Heran, Guo Yuqing, Wang Miao, Yu Lu, Han Ruxin, Liu Mengxing
College of Tea and Food Science, Xinyang Normal University, Xinyang 464000, Henan, China.
Dabie Mountain Laboratory, Xinyang 464000, Henan, China.
J Agric Food Chem. 2025 Sep 10;73(36):22196-22207. doi: 10.1021/acs.jafc.5c03082. Epub 2025 Aug 26.
In the ongoing search for more potent succinate dehydrogenase inhibitors (SDHIs) for agricultural applications, 30 pyrazole-4-carboxamide derivatives bearing a thioether group were designed and synthesized via bioisosteric replacement and scaffold-hopping based on the structure of two SDHIs lead compounds in our previous work. The antifungal efficacy of these target compounds was evaluated against five major plant pathogenic fungi, and the results indicated that the majority of the synthesized compounds exhibited strong antifungal activities, particularly against and . Among these, compound emerged as the most promising candidate, displaying exceptional antifungal potency against (EC = 0.012 μg/mL) and (EC = 0.123 μg/mL), significantly superior to boscalid (EC = 0.464 μg/mL and 0.159 μg/mL, respectively) and comparable to fluxapyroxad (EC = 0.036 μg/mL and 0.104 μg/mL). Additionally, detached leaf assays revealed that compound effectively inhibited the growth of on rice leaves and on oilseed rape leaves, achieving significant protective efficacies of 89.1% and 93.9%, respectively, at 100 μg/mL, which were superior to boscalid (68.8% and 90.5%) and comparable to fluxapyroxad (86.4% and 98.6%), indicating a promising potential for crop protection in the field, particularly for rice and oilseed rape. Furthermore, SDH enzymatic inhibition assays showed that compound exhibited potent SDH inhibition (IC = 1.30 μM), which was more effective than boscalid (IC = 1.53 μM) and close to fluxapyroxad (IC = 0.35 μM), confirming its role as an effective SDHI. SEM analysis showed that compound caused significant structural disruption and morphological damage to the hyphae of , further supporting its antifungal activity. The results of molecular docking and DFT and ESP calculations demonstrated that compound had a similar antifungal mechanism to fluxapyroxad. These findings suggested that compound held great promise as a potential SDHI candidate for protection of crops such as rice and oilseed rape, warranting further investigation.
在持续寻找用于农业应用的更高效琥珀酸脱氢酶抑制剂（SDHIs）的过程中，基于我们之前工作中两种SDHI先导化合物的结构，通过生物电子等排体替换和骨架跃迁设计并合成了30种带有硫醚基团的吡唑-4-甲酰胺衍生物。评估了这些目标化合物对五种主要植物病原真菌的抗真菌效果，结果表明大多数合成化合物表现出较强的抗真菌活性，尤其是对[此处原文缺失两种真菌名称]。其中，化合物[此处原文缺失化合物编号]成为最有前景的候选物，对[此处原文缺失两种真菌名称]显示出卓越的抗真菌效力（EC50分别为0.012 μg/mL和0.123 μg/mL），显著优于咯菌腈（EC50分别为0.464 μg/mL和0.159 μg/mL），且与氟唑菌酰胺相当（EC50分别为0.036 μg/mL和0.104 μg/mL）。此外，离体叶片试验表明，化合物[此处原文缺失化合物编号]有效抑制了水稻叶片上的[此处原文缺失一种真菌名称]和油菜叶片上的[此处原文缺失一种真菌名称]的生长，在100 μg/mL时分别达到了89.1%和93.9%的显著保护效果，优于咯菌腈（68.8%和90.5%）且与氟唑菌酰胺相当（86.4%和98.6%），表明其在田间作物保护方面具有广阔的潜力，特别是对水稻和油菜。此外，SDH酶抑制试验表明，化合物[此处原文缺失化合物编号]表现出较强的SDH抑制作用（IC50 = 1.30 μM），比咯菌腈（IC50 = 1.53 μM）更有效且接近氟唑菌酰胺（IC50 = 0.35 μM），证实了其作为有效SDHI的作用。扫描电子显微镜（SEM）分析表明，化合物[此处原文缺失化合物编号]对[此处原文缺失一种真菌名称]的菌丝体造成了显著的结构破坏和形态损伤，进一步支持了其抗真菌活性。分子对接以及密度泛函理论（DFT）和静电势（ESP）计算结果表明，化合物[此处原文缺失化合物编号]具有与氟唑菌酰胺相似的抗真菌机制。这些发现表明，化合物[此处原文缺失化合物编号]作为保护水稻和油菜等作物的潜在SDHI候选物具有很大的前景，值得进一步研究。
