Design, Synthesis, and Antifungal Activity of Trifluoromethylpyridine-Containing Amide Derivatives.

Abstract

A series of trifluoromethylpyridine-containing amide derivatives were designed and synthesized. All compounds were evaluated in vitro for antifungal activity against representative plant-pathogenic fungi. Bioassay results indicated that compounds 10o, 10t, 10x, and 10ad exhibited pronounced in vitro antifungal activities. Notably, 10ad showed an EC50 of 1.22 μg/mL against Botrytis cinerea (Bc), which was superior to those of the commercial fungicides azoxystrobin (12.84 μg/mL), procymidone (4.87 μg/mL), and Pyrimethanil (3.52 μg/mL). Compound 10ad also demonstrated in vivo antifungal efficacy against Bc, with protective and curative activities above 60% at 400 μg/mL, again surpassing these commercial fungicides. As demonstrated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), molecular docking, and enzyme activity assays, mechanistic studies suggest that 10ad disrupts organelle integrity, inhibits mycelial growth, and modulates antioxidant enzyme activities. These results indicate that 10ad is a promising lead for the development of novel crop-protection fungicides.