Design, Synthesis, and Biological Activity of Chalcone Derivatives Based on a Plant-Derived Thymol Lead

Fifty-one thymol-based chalcone derivatives were designed and evaluated for their antifungal activities against eight plant pathogenic fungi in vitro. Compound Q23 exhibited significant inhibitory activity against Valsa mali (V. mali), with an EC₅₀ value as low as 1.52 μg/mL, which was markedly superior to that of the lead compound thymol (EC₅₀ = 13.7 μg/mL) and reference fungicide azoxystrobin (Az, EC₅₀ = 21.9 μg/mL). In vivo experiments further confirmed that compound Q23 effectively controlled apple canker caused by V. mali. Preliminary mechanism studies revealed that compound Q23 induced the accumulation of reactive oxygen species in fungal cells, leading to membrane lipid peroxidation, disruption of cell membrane integrity and physiological functions, and ultimately cell death. These findings suggest that compound Q23 is a promising candidate fungicide for the control of apple canker.