四氢异喹啉衍生物的合成及体外 抗多子小瓜虫活性的研究

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

中文关键词: 四氢异喹啉衍生物  掠食体  包囊  多子小瓜虫

英文关键词: Tetrahydroisoquinoline derivatives  Theronts  Encysted tomonts  Ichthyophthirius multifiliis

中文摘要:

      合成四氢异喹啉衍生物并进行杀多子小瓜虫(Ichthyophthirius multifiliis)药效评价。以1-甲基-1,2,3,4-四氢异喹啉为起始原料，在2位的胺基上引入与环己甲酰氯、苯甲酰氯、噻吩甲酰氯、乙酰氯以及氯乙酰氯等不同的酰基进而合成5种四氢异喹啉衍生物(化合物1~化合物5)，研究其对小瓜虫掠食体和包囊的杀虫活性，并对杀虫活性物质进行安全性评价。结果显示，5种化合物均具有一定的杀虫活性，其中，化合物1 [(1-甲基-3,4-二氢异喹啉-2(1H)-基)-苯基-甲酮]的杀虫活性最强，其对多子小瓜虫掠食体4 h的100%杀灭浓度为24.0 mg/L，对包囊6 h的100%杀灭浓度为60.0 mg/L，对掠食体的半数致死浓度(LD50)为16.4 mg/L。急性毒性实验结果显示，化合物1对翘嘴红鲌(Erythroculter ilishaeformi)的48 h LD50为234.3 mg/L，其安全浓度为64.1 mg/L。研究表明，化合物1 [(1-甲基-3,4-二氢异喹啉-2(1H)-基)-苯基-甲酮]是一种具有较好开发前景的杀小瓜虫药物。

英文摘要:

      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.