Effects of a Synthetic Isoquinoline Derivative Against Ichthyophthirius multifiliis In Vivo and In Vitro in Grass Carp (Ctenopharyngodon idella)

White spot disease, caused by the parasitic <i>Ichthyophthirius multifiliis</i>, induces mortality exceeding 80% in intensive aquaculture systems, resulting in global annual losses of >$1 billion. Current chemical controls (e.g., formaldehyde) face environmental persistence and drug resistance challenges. This study developed a synthetic isoquinoline derivative, BHTCA (s)-2-tert-butoxycarbonyl-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), as a biodegradable alternative against <i>I. multifiliis</i> in grass carp (<i>Ctenopharyngodon idella</i>). In vitro assays revealed stage-selective efficacy: theronts exhibited higher susceptibility (EC₅₀ = 0.10 mg/L at 4 h) than tomonts (EC₅₀ = 0.40 mg/L at 24 h), with BHTCA disrupting ciliary structures and compromising cyst integrity. In vivo trials (0.6 mg/L) reduced parasite loads by 78.1% and host mortality by 66.7% versus untreated controls. Acute toxicity tests confirmed a high therapeutic index (LC₅₀ = 16.75 mg/L; >167× effective concentration). With demonstrated efficacy, low production cost, and minimal eco-toxicity, BHTCA presents a sustainable strategy for Ichthyophthiriasis management in aquaculture.