Design, Synthesis, and Fungicidal Activity Evaluation of 2,6-Dinitrophenol Derivatives

In search of novel fungicides, 35 target compounds were prepared through structural modifications at the phenolic hydroxyl, methyl, and nitro positions of 3,4-dimethyl-2,6-dinitrophenol. Several compounds exhibited promising antifungal activities against various phytopathogenic fungi, among which compound 5a demonstrated the most potent activity, with IC50 values of 0.67 mg/L against Rhizoctonia solani, 3.86 mg/L against Gibberella zeae, 2.64 mg/L against Pyricularia oryzae, 0.74 mg/L against Phytophthora infestans, 2.29 mg/L against Botrytis cinerea, and 3.75 mg/L against Ralstonia solanacearum. Compound 5a exhibited good in vivo preventive and therapeutic effects against Rhizoctonia solani and Pyricularia oryzae. Further mechanistic studies revealed that compound 5a could increase mycelial cell membrane permeability, induce mycelial morphological shrinkage, and elevate intracellular reactive oxygen species levels. Moreover, the phytotoxicity of compound 5a on rice seed germination and its acute toxicity to zebrafish were significantly lower than those of fluazinam. These findings suggest that compound 5a holds promising potential for further development as an antifungal agent.