Synthesis of 1-Methyl-1,2,3,4-Tetrahydroisoquinoline Derivatives and Its Antiparasitic Activity Against Ichthyophthirius multifiliis in vitro

Abstract:

To develop novel antiparasitic agents, five 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives were designed and synthesized. Cyclohexanecarboxylic acid chloride, benzoyl chloride, thiophene formyl chloride, acetylchloride, and chloroacetyl chloride were introduced into the 2-position of amido in the initial compound-1-methyl-1,2,3,4-tetrahydroisoquinoline. The chemical structures of all five synthesized compounds were identified by comparing spectral data (EI-MS, 1H NMR, and 13C NMR) with literature values, and their antiparasitic activity against Ichthyophthirius multifiliis theronts and encysted tomonts in vitro were also evaluated. Additionally, the acute toxicity of the five synthesized compounds against Erythroculter ilishaeformis was evaluated. The results indicated that all five synthesized compounds showed promising antiparasitic activity against I. multifiliis theronts and encysted tomonts; however, compound 1 [cyclohexyl-(1-methyl-3,4-dihydroiso-quinoline)-ketone] with the cyclohexanecarboxylic acid chloride group showed better antiparasitic activity than the other four compounds. The in vitro tests revealed that compound 1 could be 100% effective against theronts at a concentration of 24.0 mg/L. The median lethal dose (LD50) of compound 1 against theronts at 4 h was 16.4 mg/L. All encysted tomonts were killed when the concentration of compound 1 was 60.0 mg/L. The LD50 of compound 1 for E. ilishaeformis was 234.3 mg/L with a safe concentration of 64.1 mg/L. This study firstly demonstrated that compound 1 has potent antiparasitic efficacy against I. multifiliis, and it could be a good candidate drug for chemotherapy and control of I. multifiliis infections.