Structure - Guided design of arctigenin derivatives against infections of Gyrodactylus kobayashii

Gyrodactylosis is a widespread parasitic illness that affects fish in both farming and natural environments. The current chemotherapy approaches are not always satisfactory, so the development of new anthelmintic agents is necessary. Arctigenin, a natural lignan found in various plants, possesses a multitude of biological activities. Previous research has demonstrated that arctigenin targets the protein myosin in Gyrodactylus kobayashii. Building upon this interaction, we designed 31 derivatives of arctigenin using Discovery Studio. The ester derivatives exhibited significant anthelmintic activity, with C-21 displaying the highest activity, boasting an EC50 of 0.4 mg/L. Furthermore, we conducted an investigation into the mechanism by which C-21 affects the parasite and discovered that it disrupts the muscular structure of the parasite's body surface, thus inhibiting its energy production and myosin expression, ultimately leading to the parasite's demise. In conclusion, C-21 exhibits promising potential as an agent for controlling Gyrodactylus kobayashii infection.