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(LD_(50))为16.4mg/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 LD_(50)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。
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 13 C 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.
作者
姚嘉赟
徐洋
袁雪梅
蔺凌云
尹文林
潘晓艺
郝贵杰
沈锦玉
YAO Jiayun;XU Yang;YUAN Xuemei;LIN Lingyun;YIN Wenlin;PAN Xiaoyi;HAO Guijie;SHEN Jinyu(Key Laboratory of Healthy Freshwater Aquaculture,Ministry of Agriculture and Rural Affairs,Key Laboratory of Fish Health and Nutrition of Zhejiang Province,Zhejiang Institute of Freshwater Fisheries,Huzhou 313001)
出处
《渔业科学进展》
CSCD
北大核心
2019年第1期141-146,共6页
Progress in Fishery Sciences
基金
浙江省公益技术应用研究项目(LGN18C190005
2014C32055)
浙江省科技计划项目(2017F30034)共同资助~~
关键词
四氢异喹啉衍生物
掠食体
包囊
多子小瓜虫
Tetrahydroisoquinoline derivatives
Theronts
Encysted tomonts
Ichthyophthirius multifiliis
