Design, Synthesis, Antifungal Evaluation, and Molecular Docking of Novel 1,2,4-Triazole Derivatives Containing Oxime Ether and Cyclopropyl Moieties as Potential Sterol Demethylase Inhibitors

In a search for novel sterol demethylase inhibitors (DMIs), a series of 1,2,4-triazole derivatives containing oxime ether and cyclopropyl moieties were designed by the bioactive substructure combination assisted by virtual molecular docking. The above target compounds were characterized by the 1H NMR, 13C NMR, 19F NMR, and HR-MS spectra. The antifungal evaluation against Rhizoctonia solani (Rs), Fusarium graminearum (Fg), and Botrytis cinerea (Bc) indicated that most of target compounds possessed remarkable inhibitory activities against the above tested fungi. Significantly, the compound 5k exhibited outstanding anti-Fg activity with the EC50 value of 1.22 μg/mL in vitro, and the protective effect of 59.45% in vivo at 200 μg/mL. Further investigation revealed that compound 5k evidently inhibited Fg spore germination and caused some wrinkles and dents on the surface of mycelia. Molecular docking showed that compound 5k bound with the target protein FgCYP51 via coordination, hydrogen bonding and stacking interactions that were similar, but slightly different than the interactions of tebuconazole with FgCYP51. These research results suggested that the target compounds have value for the further structural optimization of novel triazole fungicides.