To continue our ongoing studies on discovery of new potent antifungal leads, 43 novel pyrazole-aromatic containing carboxamides were rationally designed and synthesized. Bioassays indicated that most target compounds displayed good in vitro antifungal activities against Botrytis cinerea, Rhizoctonia cerealis and Sclerotinia sclerotiorum and in vivo antifungal activity against R. solani. Compound 11ea exhibited the most significant in vitro activity against R. cerealis (EC₅₀ = 0.93 μg/mL) with about 2-fold more potent than a previously reported lead compound A1 (EC₅₀ = 2.01 μg/mL), and about 11-fold more potent than the positive control/commercial succinate dehydrogenase inhibitor thifluzamide (EC₅₀ = 23.09 μg/mL). Structure-activity relationship analysis and molecular docking simulations indicated that the presence of difluoromethyl pyrazole-(m-benzene) carboxamide scaffold obviously increased the antifungal activity. The further enzymatic bioassay showed that both thifluzamide and compound 11ea displayed excellent SDH inhibitory effects, and fluorescence quenching analysis suggested that they may share the same target SDH.

为了继续我们正在进行的有关发现新的有效抗真菌药物的研究，我们合理设计和合成了43种新颖的吡唑-芳香族含羧酰胺。生物测定表明，大多数的目标化合物表现出良好的体外抗真菌活性对抗灰葡萄孢，禾谷丝核和核盘菌和体内抗真菌活性纹枯病菌。化合物11ea表现出最显著体外对抗活性R.禾谷（EC ₅₀  = 0.93微克/毫升）用约2倍比以前报道的铅化合物更有效A1（EC ₅₀ = 2.01μg/ mL），并且比阳性对照/商业琥珀酸脱氢酶抑制剂硫氟酰胺（EC ₅₀  = 23.09μg/ mL）强约11倍。结构-活性关系分析和分子对接模拟表明，二氟甲基吡唑的存在（米-苯）甲酰胺的支架显着升高的抗真菌活性。进一步的酶促生物测定显示，噻氟甲酰胺和化合物11ea均显示出优异的SDH抑制作用，荧光猝灭分析表明它们可能共享相同的目标SDH。