Screening of candidate antiparasitic drugs against Sparicotyle chrysophrii: A phenotypic drug discovery approach.

Sparicotyle chrysophrii is a blood-feeding ectoparasite that poses a significant threat to the farming of gilthead seabream (Sparus aurata), a species of high economic relevance in Mediterranean aquaculture. There is an urgent need for effective, safe, and practical antiparasitic treatments to control these infections. In this study, a phenotypic screening approach was applied to identify compounds active against S. chrysophrii. A panel of reference anthelmintic drugs was selected and used as query molecules in a computational ligand-based virtual screening. The parasiticidal efficacy and potency of the reference drugs, together with compounds selected based on topological indexes, were assessed against adult S. chrysophrii using an in vitro dose-response assay. Among the tested compounds, three salicylanilide derivatives exhibited the highest short-term efficacy, showing the lowest lethal doses 50 (LD50): niclosamide (LD50=0.12 µM), closantel (LD50=2.3 µM), and ME1.62 (LD50=0.09 µM). Niclosamide, one of the most potent compounds identified, demonstrated a parasiticidal activity more than 11,000-times greater than praziquantel (LD50=1.43 mM), a reference chemotherapeutic agent commonly used against fish polyopisthocotylean parasites.