Design, Synthesis and Antifungal Activity of Nootkatone Derivatives Containing Acylhydrazone and Oxime Ester

Abstract In an attempt to search for new natural products‐based antifungal agents, fifty‐three nootkatone derivatives were designed, synthesized, and evaluated for their antifungal activity against Phytophthora parasitica var nicotianae , Fusarium oxysporum , Fusarium graminearum and Phomopsis sp . by the mycelium growth rate method. Nootkatone derivatives N17 exhibited good inhibitory activity against Phomopsis. sp . with EC 50 values of 2.02 μM. The control effect of N17 against Phomopsis. sp . on kiwifruit showed that N17 exhibited a good curative effect in reducing kiwifruit rot at the concentration of 202 μM(100×EC 50 ), with the curative effect of 41.11 %, which was better than commercial control of pyrimethanil at the concentration of 13437 μM(100×EC 50 ) with the curative effect of 38.65 %. Phomopsis. sp . mycelium treated with N17 showed irregular surface collapse and shrinkage, and the cell membrane crinkled irregularly, vacuoles expanded significantly, mitochondria contracted, and organelles partially swollen by the SEM and TEM detected. Preliminary pharmacological experiments show that N17 exerted antifungal effects by altering release of cellular contents, and altering cell membrane permeability and integrity. The cytotoxicity test demonstrated that N17 showed almost no toxicity to K562 cells. The presented results implied that N17 may be as a potential antifungal agents for developing more efficient fungicides to control Phomopsis sp .