Novel 1,2,4-Triazole Derivatives Containing a Benzenesulfonamide Moiety as Potential Antifungal Agents for Controlling Postharvest Soft Rot in Kiwifruit.

Fungal diseases in plants have emerged as a major threat to global agriculture, leading to substantial economic losses. In response to the growing need for effective antifungal agents, we present here a series of 1,2,4-triazole derivatives incorporating a benzenesulfonamide moiety and explore their antifungal potential. Among these, compound 4s against Phomopsis sp. (PS) achieved an EC50 value of 0.15 μg/mL, outperforming the reference fungicide tebuconazole (0.18 μg/mL). In protective and curative assays on kiwifruit leaves and fruits, the efficacy also surpassed that of tebuconazole. Cell physiology investigations revealed that compound 4s caused disruption of cell morphology and impairment of cell membrane integrity. Transcriptomic and proteomic analyses showed that CYP51, a typical azole target functioning in ergosterol biosynthesis, was outstandingly highly expressed. Additionally, molecular docking and enzymatic assays confirmed that compound 4s can readily enter the substrate pocket of CYP51 and inhibit its activity. These findings indicate that compound 4s, as a potent fungicidal candidate with the potential to address challenges in agricultural pathogen management, exerts antifungal activity by inhibiting the key enzyme CYP51 in the ergosterol biosynthetic pathway.