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 <b>4s</b> against <i>Phomopsis</i> 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 <b>4s</b> 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 <b>4s</b> can readily enter the substrate pocket of CYP51 and inhibit its activity. These findings indicate that compound <b>4s</b>, 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.