Synthesis, Antifungal Activity, and Potential Mechanism of Natural Product Pogostone Derivatives Containing an Acylhydrazone Scaffold

The current study designed and synthesized a series of acylhydrazone derivatives based on the natural product pogostone. Among them, compound 2a15 exhibited potent fungicidal activity against Valsa mali (V. mali) (EC50 = 0.34 μg/mL) and Sclerotinia sclerotiorum (S. sclerotiorum) (EC50 = 0.45 μg/mL). At 200 μg/mL, 2a15 exhibited 81.26 and 82.08% efficacies against V. mali and S. sclerotiorum, respectively. Qualitative structure-activity analysis showed that when the benzene ring was substituted by a bromine atom, chlorine atom, or electron-withdrawing group, compounds with the substituent group in the para position displayed the best activity. Compound 2a15 treatment induced an explosion of ROS, unbalanced mitochondrial membrane potential, and declined activities of pectinase and SDH in V. mali. Moreover, the expression of the pectinase gene was significantly upregulated. Importantly, molecular docking revealed that 2a15 had a strong affinity with SDH-B. According to density functional theory, more dispersed lowest unoccupied molecular orbital (LUMO) distribution and a low energy gap between the LUMO and HOMO were beneficial for activity improvement.