3‑Hydroxy-2-oxindole Derivatives Containing Sulfonamide Motif: Synthesis, Antiviral Activity, and Modes of Action

3-Hydroxy-2-oxindole motif constitutes a core structure in numerous natural products and imparts notable biological activities. Here, we describe the design and synthesis of four series of novel 3-substituted-3-hydroxy-2-oxindole derivatives containing sulfonamide moiety along with their antiviral activities against potato virus Y (PVY). Compound 10b displayed optimal antiviral activity and superior anti-PVY activity compared with the lead compound and commercial Ningnanmycin in terms of curative and protective effects. Additionally, 10b considerably inhibited PVY systemic infection in Nicotiana benthamiana. Physiological and biochemical analyses revealed that the activities of the four crucial defense-related enzymes increased in the tobacco plant following treatment with 10b. RNA-sequencing analysis revealed that 10b substantially induced the upregulation of 38 differentially expressed genes, which were enriched in the photosynthesis pathway. These findings suggest that 10b is a promising antiviral agrochemical that can effectively control PVY infection and trigger plant host immunity to develop virus resistance. This study provides novel molecular entities and ideas for developing new pesticides.