Trifluoromethylpyridine piperazine derivatives: synthesis and anti-plant virus activity

The cucumber mosaic virus (CMV) is well-known for its expansive host range and distribution, resulting in a detrimental effect on agricultural production, thus making it imperative to implement measures for its control.

Novel compounds S1-S28 were synthesized by connecting trifluoromethyl pyridine, amide and piperazine scaffolds. Bioassays indicated that most of the synthesized compounds exhibited good curative effects against CMV, with half maximal effective concentration (EC₅₀ ) values of compounds S1, S2, S7, S8, S10, S11, S15, and S28 being 119.6, 168.9, 197.6, 169.1, 97.9, 73.9, 224.4, and 125.2 μg mL^-1 , respectively, which were lower than the EC₅₀ of ningnanmycin (314.7 μg mL^-1 ). Compounds S5 and S8 exhibited protective activities with EC₅₀ of 170.8 and 95.0 μg mL^-1 , respectively, which were lower than ningnanmycin at 171.4 μg mL^-1 . The inactivation activities of S6 and S8 at 500 μg mL^-1 were remarkably high at 66.1% and 78.3%, respectively, surpassing that of ningnanmycin (63.5%). Additionally, their EC₅₀ values were more favorable at 22.2 and 18.1 μg mL^-1 , respectively, than ningnanmycin (38.4 μg mL^-1 ). And molecular docking and molecular dynamics simulation showed compound S8 had better binding with CMV-coat protein, providing a possible explanation for the anti-CMV activity of compound S8.

Compound S8 showed a strong binding affinity to CMV-coat protein and impacted the self-assemble of CMV particles. Compound S8 could be a potential lead compound for discovering a new anti-plant virus candidate. © 2023 Society of Chemical Industry.