Development of Imidazo[1,2‑a]pyridines Containing Sulfonyl Piperazines as Potential Antivirals against Tomato Spotted Wilt Virus

Mesoionic structures have become important advancements in recent agrochemical design. However, their potential beyond serving as excellent insecticides remains unexplored with limited reports available. Herein, a series of imidazo­[1,2-a]­pyridine mesoionics were developed by structurally incorporating sulfonyl piperazine moieties into imidazo­[1,2-a]­pyridines. Many of the obtained derivatives demonstrated bioactivity against tomato spotted wilt virus (TSWV) in bioassays. In particular, compound Z40, identified via three-dimensional quantitative structure activity relation models, displayed encouraging protective performance (half-maximal effect concentration = 252 μg/mL) compared to the positive controls ningnanmycin (332 μg/mL) and vanisulfane (523 μg/mL). Through defense enzyme assays, real-time quantitative polymerase chain reaction, and proteomics analysis, Z40 was identified as a plant immunomodulator that promotes defense enzyme activity and the mediates oxidative phosphorylation pathway, enabling plants to resist TSWV. We expect this study to help expand the possibilities of mesoionic compounds.