Discovery of Imidazolecarboxylic Acid Oxime Esters as Potential Fungicides and Novel Sterol Biosynthesis Inhibitors

Abstract To discover fungicidal candidates with potent antifungal activity, a series of novel imidazolecarboxylic acid oxime ester derivatives were designed and synthesized based on our previous research. Their antifungal activities were systematically evaluated, and the preliminary mechanism of action was investigated. Compound 7j exhibited outstanding inhibitory activity against Botrytis cinerea, with a median effective concentration (EC50) value of 0.34 μg/mL, which was markedly superior to the positive control trifloxystrobin (EC50 = 11.30 μg/mL). Notably, at 200 μg/mL, the protective and curative efficacies of compound 7j against B. cinerea on potted tomato leaves reached 93.8% and 91.9%, respectively, comparable to boscalid (95.4% and 85.9%). Preliminary mechanistic studies indicated that compound 7j may suppress sterol 14α-demethylase (CYP51) activity within the sterol biosynthesis pathway, impairing fungal membrane integrity, perturbing cellular homeostasis, and ultimately inhibiting fungal growth. Featuring a simple structure, facile synthesis and excellent bioactivity, compound 7j possesses promising prospects for agrochemical development.