Novel Cyclized Derivatives of Ferulic Acid as Potential Antiviral Agents through Activation of Photosynthesis.

To further develop new antiviral agents, several novel cyclized derivatives of ferulic acid were designed and synthesized. Their antiviral activities were evaluated against the cucumber mosaic virus (CMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV). The results showed that some ferulic acid derivatives exhibited desirable antiviral activities. Particularly, compound 5e exhibited excellent protective activities against CMV, PMMoV, and TSWV, with EC50 values of 167.2, 102.5, and 145.8 μg mL-1, respectively, which were superior to those obtained for trans-ferulic acid (581.7, 611.2, and 615.4 μg mL-1), dufulin (312.6, 302.5, and 298.2 μg mL-1), and ningnanmycin (264.3, 282.5, and 276.5 μg mL-1). Thereafter, the protective mechanisms of 5e were evaluated through photosynthesis evaluation, transcriptome profiling, and proteomic analysis. The results indicated that 5e significantly activated the expression levels of photosynthesis-related regulatory genes and proteins in tobacco plants and promoted the accumulation of defense molecules to resist viral infection. Thus, the findings of this study indicated that novel cyclized ferulic acid derivatives are potential antiviral agents that act via regulating photosynthesis in the host.