Synthesis of Novel Antiviral Ferulic Acid-Eugenol and Isoeugenol Hybrids Using Various Link Reactions.

To develop novel antiviral agents, some novel conjugates between ferulic acid and eugenol or isoeugenol were designed and synthesized by the link reaction. The antiviral activities of compounds were evaluated using the half leaf dead spot method. Bioassay results showed acceptable antiviral activities of some conjugates against the tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Compounds , , , and showed remarkable curative, protective, and inactivating effects on TMV and CMV at 500 μg mL. Notably, these compounds exhibited excellent protective effects on TMV and CMV. The EC values of compounds , , , and against TMV were 180.5, 169.5, 211.4, and 135.5 μg mL, respectively, and those against CMV were 210.5, 239.1, 218.4, and 178.6 μg mL, respectively, which were superior to those of ferulic acid (471.5 and 489.2 μg mL), eugenol (456.3 and 463.2 μg mL), isoeugenol (478.4 and 487.5 μg mL), and ningnanmycin (246.5 and 286.6 μg mL). Then, the antiviral mechanisms of compound were investigated by determining defensive enzyme activities and multi-omics analysis. The results indicated that compound resisted the virus infection by enhancing defensive responses inducing the accumulation of secondary metabolites from the phenylpropanoid biosynthesis pathway in tobacco.