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 the search for novel sterol demethylase inhibitors (DMIs), a series of 1,2,4-triazole derivatives containing oxime ether and cyclopropyl moieties were designed using the bioactive substructure combination assisted by virtual molecular docking. The above-mentioned target compounds were characterized using the 1 H NMR, 13 C NMR, 19 F NMR, and HR-MS spectra. The antifungal evaluation against Rhizoctonia solani ( Rs ), Fusarium graminearum ( Fg ), and Botrytis cinerea ( Bc ) indicated that most of the target compounds exhibited remarkable inhibitory activities against the above-mentioned tested fungi. Significantly, the compound 5k exhibited outstanding anti- Fg activity with an EC 50 value of 1.22 μg mL −1 in vitro , and a protective effect of 59.45% in vivo at 200 μg mL −1 . 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 Fg CYP51 via coordination, hydrogen bonding and stacking interactions that were similar, but slightly different from the interactions of tebuconazole with Fg CYP51. These research results suggested that the target compounds are valuable for the further structural optimization of novel triazole fungicides. A series of novel triazole derivatives containing oxime ether and cyclopropyl moieties were designed and synthesized. Some compounds exhibited remarkable antifungal activities. The molecular docking of compound 5k with Fg CYP51 was investigated.