Synthesis and fungicidal activity of novel 1,1-diaryl-2-azolylethanols with a pyridine moiety.

To investigate the effect of pyridine heterocycle on the activity of triazole alcohol fungicides, 31 pyridine-containing 2-azolyl-1,1-diarylmethanol derivatives were designed and synthesized using flutriafol as the lead compound and pyridine diaryl ketone molecular building blocks as the basis. The in vitro fungicidal activity against 10 plant pathogenic fungi was determined, and the results showed that the target compounds exhibited broad-spectrum inhibitory effects on the tested pathogens. Among them, the imidazole-substituted compounds I-24, I-26 and I-27 displayed remarkable fungicidal activity against Sclerotinia sclerotiorum, Phytophthora capsici, Pythium aphanidermatum, Botrytis cinerea and other fungi. The EC₅₀ values of compound I-24 against various pathogens were as low as 3.55 ~ 15.46 μg/mL, and its in vivo curative activity against Botrytis cinerea on tomato fruits was comparable to that of the positive control flutriafol. Structure-activity relationship analysis revealed a positive correlation between the hydrophobicity of the compounds and their fungicidal activity. The replacement of cyclohexyl with benzene ring and the introduction of substituents at the 2-position of the benzene ring exerted a positive effect on the activity. Triazole and imidazole derivatives showed similar overall activity, with some imidazole-substituted compounds exhibiting superior activity. Molecular docking studies further elucidated the binding mechanism of the compounds to the 14α-demethylase of Fusarium graminearum and the reasons for the differences in their biological activities.