Discovery of Potential Antifungal Agents: Chalcone Derivatives Containing Thiourea and Piperidine Moieties

Abstract

Twenty-two chalcone derivatives containing thiourea and piperidine moieties were synthesized. The in vitro antifungal activities of these compounds against nine fungi were evaluated. The results demonstrated that a majority of these compounds exhibited exceptional antifungal activities. Especially, K2 displayed the most potent fungicidal activity against Phytophthora capsici (P. capsici), with a half-effective concentration (EC₅₀) of 5.96 μg/mL, surpassing that of the control drug azoxystrobin (Az, 25.2 μg/mL). The in vivo antifungal experiments of K2 were conducted on pepper leaves and fruits. It exhibited significant protective efficacy against P. capsici in pepper leaves (95.3%) at 200 μg/mL, which surpassed that of Az (79.0%). Morphological investigations utilizing scanning electron microscopy (SEM) and fluorescence microscopy (FM) unveiled the disruptive impact of K2 on P. capsici mycelium. Moreover, mechanistic studies have demonstrated that K2 exhibited the capacity to disrupt the integrity of the cellular membrane in pathogenic fungi, influence lipid peroxidation processes within the membrane, and induce cellular content release. These experimental findings provided a new idea for effectively preventing plant fungal diseases and developing novel green chemical pesticide products.