A novel antiparasitic medicine from coumarins against Dactylogyrus intermedius infection in goldfish using 3D-QSAR model.

Dactylogyrus is one of the most serious parasites in aquaculture, resulting in devastating disease for severe economic impacts. In order to further increase the anthelmintic activity of coumarins, statistically valid three-dimensional quantitative structure-activity relationship (3D-QSAR) models was conducted by comparative molecular field analysis (CoMFA) to obtain better novel and promising anthelmintic coumarins within a total of 52 compounds in this study. By served C24 and C41 as template molecules, the steric and electrostatic fields of comparative molecular field analysis (CoMFA) showed a good correlation and predictive power, which was verified the model reliable. Based on the models, eight newly coumarin derivatives Q1 - Q8 were designed and synthesized, and Q1 , Q2 , Q6 and Q7 showed better antiparasitic activities (the EC 50 values ranged from 0.18 to 0.26 mg/L) than that of coumarin C24 and C41 (the EC 50 values of 0.85 and 0.80 mg/L). By comparing the therapeutic index (TI), the order is the potency of Q4 > Q5 > Q7 > mebendazole > Q2 > Q6 > praziquantel > Q1 > Q3 , which suggests that Q4 should be a viable way for controlling Dactylogyrus infection. Meanwhile, Q4 with a high stability in aquacultural water in immersion suppressed horizontal transmission of Dactylogyrus. These results will be contributed to further improve drug potency on aquacultural parasite control. • 3D-QSAR models was conducted to obtain better novel and promising anthelmintic coumarins. • Four coumarins from the model exhibited excellent antiparasitic activity against Dactylogyrus infection. • Coumarin Q4 suppressed horizontal transmission of Dactylogyrus. [ABSTRACT FROM AUTHOR]