Novel Chalcone Derivatives Containing Pyrazole: Synthesis, Antifungal Activity Evaluation, and Mechanism of Action against Phomopsis sp.

Abstract

16 chalcone derivatives containing pyrazole were synthesized. The antifungal activity of the target compounds against 8 pathogenic fungi was measured. The results of the in vitro antifungal activity test indicated that the EC₅₀ of Z10 for Phomopsis sp. (P.s.) was 12.5 μg/mL, which was better than those of the control prescription drugs azoxystrobin (Az, 24.9 μg/mL) and flupidazamide (Fl, 282.6 μg/mL). The molecular docking, density functional theory (DFT) calculation, and molecular electrostatic potential results showed that the binding affinity of Z10 to the SDH protein was better than that of Fl. The results of scanning electron microscopy (SEM) and fluorescence microscopy (FM) showed that Z10 disrupted the fullness of the pathogenic fungal membrane, causing the cell membrane to curve, fork, and fold and affecting the normal growth of mycelium. Further studies found that the change of membrane integrity of pathogenic fungi led to the leakage of cytoplasmic contents and the increase of malondialdehyde (MDA) content.