A series of new fungicides that can
inhibit the succinate dehydrogenase
(SDH) was classified and named as SDH inhibitors by the Fungicide
Resistance Action Committee in 2009. To develop more potential SDH
inhibitors, we designed and synthesized a novel series of N-(substituted pyridine-4-yl)-1-(substituted phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide derivatives, 4a–4i, namely, 5a–5h, 6a–6h, and 7a–7j. The bioassay results demonstrated that some title compounds
exhibited excellent antifungal activity against four tested phytopathogenic
fungi (Gibberella zea, Fusarium oxysporum, Cytospora mandshurica, and Phytophthora infestans). The
EC50 values were 1.8 μg/mL for 7a against G. zeae, 1.5 and 3.6 μg/mL for 7c against F. oxysporum and C. mandshurica, respectively, and 6.8 μg/mL
for 7f against P. infestans. The SDH enzymatic activity testing revealed that the IC50 values of 4c, 5f, 7f, and
penthiopyrad were 12.5, 135.3, 6.9, and 223.9 μg/mL, respectively.
The molecular docking results of this series of title compounds with
SDH model demonstrated that the compounds could completely locate
inside of the pocket, the body fragment formed H bonds, and the phenyl
ring showed a π–π interaction with Arg59, suggesting
that these novel 5-trifluoromethyl-pyrazole-4-carboxamide derivatives
might target SDH. These results could provide a benchmark for understanding
the antifungal activity against the phytopathogenic fungus P. infestans and prompt us to discover more potent
SDH inhibitors.