Ferulic acid derivatives with piperazine moiety as potential antiviral agents

Background Plant virus diseases are difficult to control and severely threaten the productivity of crops, which leads to huge financial losses. To discover the new antiviral drugs, 34 novel ferulic acid derivatives with piperazine moiety were synthesized, and the antiviral activities were systematically screened as well. Results Bioassay results indicated that most of the target compounds had outstanding antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. In particular, compound E2 exhibited remarkable curative activities to TMV and CMV with EC50 values of 189.0 and 401.7 μg/mL compared to those for ningnanmycin (387.0, 519.3 μg/mL) and ribavirin (542.1, 721.5 μg/mL). And then the mechanisms of compound E2 were studied by chlorophyll content, differentially expressed proteins and genes tests. Conclusion The excellent antiviral activity of compound E2 was closely associated with the increase in host photosynthesis, which was confirmed by chlorophyll content, differentially expressed proteins and genes assays. Compound E2 can be considered as a lead structure for the discovery of new antiviral agents. © 2022 Society of Chemical Industry. Novel ferulic acid derivatives with piperazine moiety were synthesized. Compound E2 had excellent antiviral activity due to enhanced photosynthesis by regulating the expressed levels of genes and proteins.