Synthesis and antifungal activity evaluation of flavonol derivatives containing an imidazolidinone moiety

Phytopathogenic fungi pose a major threat to crop production and food safety, driving an urgent need for novel, highly effective, and environmentally friendly antifungal agents. To address this need, 22 flavonol derivatives incorporating imidazolidinone pharmacophore were designed and synthesized, and their antifungal activities were systematically evaluated against seven plant pathogenic fungi. Among them, H7 was selected as a candidate compound due to its superior activity, exhibiting a half-maximal effective concentration (EC₅₀) value of 10.1 μg/mL against Phomopsis sp., superior to the reference fungicides azoxystrobin (Az: EC₅₀ = 38.0 μg/mL) and fluopyram (Fl: EC₅₀ = 177.3 μg/mL). In vivo assays on kiwifruit demonstrated that at 200 μg/mL, H7 provided curative and protective efficacies of 60.5 and 67.1%, respectively, both superior to those of Az (39.5 and 44.0%). Preliminary mechanistic investigations suggested that the antifungal activity of H7 is associated with disruption of cell membrane integrity and inhibition of succinate dehydrogenase activity. Collectively, these findings indicate that H7 could serve as a lead compound for the development of novel fungicides against kiwifruit soft rot.