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

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, <b>K2</b> displayed the most potent fungicidal activity against <i>Phytophthora capsici</i> (<i>P. capsici</i>), with a half-effective concentration (EC₅₀) of 5.96 μg/mL, surpassing that of the control drug azoxystrobin (<b>Az</b>, 25.2 μg/mL). The in vivo antifungal experiments of <b>K2</b> were conducted on pepper leaves and fruits. It exhibited significant protective efficacy against <i>P. capsici</i> in pepper leaves (95.3%) at 200 μg/mL, which surpassed that of <b>Az</b> (79.0%). Morphological investigations utilizing scanning electron microscopy (SEM) and fluorescence microscopy (FM) unveiled the disruptive impact of <b>K2</b> on <i>P. capsici</i> mycelium. Moreover, mechanistic studies have demonstrated that <b>K2</b> 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.