Synthesis and Antiparasitic Activity against Protozoan Parasite Ichthyophthirius multifiliis of N-Substituted-Tetrahydroisoquinoline Derivatives
YAO Jiayun1, ZHANG Chengsai2, YIN Wenlin1, LIN Lingyun1, PAN Xiaoyi1, CAO Zheng1, LIU Yihan1, XIA Yanchun1, SHEN Jinyu1
1. 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, China; 2. College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Key Laboratory of Animal Production and Product Quality Safety, Ministry of Education, Jilin Agricultural University, Changchun 130118, China
Abstract：Three N-substituted-tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their antiparasitic activity against protozoan parasite Ichthyophthirius multifiliis in vitro. The toxicity of the synthesized N-substituted-tetrahydroisoquinoline derivatives was also evaluated to develop novel antiparasitic agents against the protozoan parasite. The results showed that there was promising antiparasitic activity against I. multifiliis theronts and encysted tomonts in vitro in all the three synthesized compounds, with the maximal activity against I. multifiliis in compound 1 (2-methylamino-1,2,3,4-tetrahydroisoquinoline-formonitrile). The compound 1 had 100% effective against theronts at concentration of 20.0 mg/L in 4 h, with the median lethal concentration (LC50) of 11.6 mg/L. All dead encysted tomonts were observed in compound 1 at concentration of 40.0 mg/L, with the compound 1 48 h LC50 of 62.78 mg/L for topmouth culter Erythroculter ilishaeformis. The findings indicated that compound 1 (2-methylamino-1,2,3,4-tetrahydroisoquinoline-formonitrile) was useful in aquaculture for control of I. multifiliis due to high antiparasitic efficacy against I. multifiliis with low toxicity.
[1]沈韫芬.原生动物学[M].北京:科学出版社,1999:455-456. [2]Lom J, Dykova I. Protozoan parasites of fishes [J]. Developments in Aquaculture and Fisheries Science,1992,26(12):1-315. [3]Ewing M S, Kocan K M. Invasion and development strategies of Ichthyophthirius multifilis, a parasitic ciliate of fish[J]. Parasitology Today,1992,8(6):204-208. [4]Klesius P, Rogers W. Parasitisms of catfish and other farm-raised food fish [J]. Journal of the American Veterinary Medical Association,1995,207(11):1473-1478. [5]Hines R S, Spira D T. Ichthyophthiriasis in the mirror carp Cyprinus carpio (L.) V: acquired immunity [J]. Journal of Fish Biology,1974,6(4):373-378. [6]Wahli T, Schmitt M, Meier W. Evaluation of alternatives to malachite green oxalate as a therapeutant for Ichthyophthiriosis in rainbow trout, Oncorhynchus mykiss [J]. Journal of Applied Ichthyology,1993,9(3/4):237-249. [7]Rowland S J, Mifsud C, Nixon M, et al. Use of formalin and copper to control ichthyophthiriosis in the Australian freshwater fish silver perch (Bidyanus bidyanus Mitchell)[J].Aquaculture Research,2008,40(1):44-54. [8]Straus D L, Hossain M M, Clark T G, et al. Strain differences in Ichthyophthirius multifiliis to copper toxicity[J]. Disease of Aquatic Organism,2009,83(3):31-36. [9]Lahnsteiner F, Weismann T. Treatment of ichthyophthiriasis in rainbow trout and common carp with common and alternative therapeutics[J]. Journal of Aquatic Animal Health,2007,19(3):186-194. [10]Straus D L, Meinelt T. Acute toxicity of peracetic acid (PAA) formulations to Ichthyophthirius multifiliis theronts[J].Parasitology Research,2009,104(5):1237-1241. [11]Heinecke R D, Buchmann K. Control of Ichthyophthirius multifiliis using a combination of water filtration and sodium percarbonate: dose-response studies[J]. Aquaculture,2009,288(3):32-35. [12]Shinn A P, Picón-Camacho S M, Bron J E, et al. The anti-protozoal activity of bronopol on the key life-stages of Ichthyophthirius multifiliis Fouquet, 1876 (Ciliophora)[J].Veterinary Parasitology,2012,186(3/4):229-236. [13]Picón-Camacho S M, Taylor N G, Bron J E, et al. Effects of long duration, low dose bronopol exposure on the control of Ichthyophthirius multifiliis (Ciliophora), parasitising rainbow trout (Oncorhynchus mykiss Walbaum) [J]. Veterinary Parasitology,2012,186(3/4):237-244. [14]Ling F, Wang J G, Liu Q F, et al. Prevention of Ichthyophthirius multifiliis infestation in goldfish (Carassius auratus) by potassium ferrate(Ⅵ) treatment[J].Veterinary Parasitology,2010,168(3/4):212-216. [15]姚嘉赟,徐洋,袁雪梅,等.丁香酚的分离及其杀多子小瓜虫活性研究[J].水产科学,2016,35(6):669-674. [16]Yao J Y, Shen J Y, Li X L, et al. Effect of sanguinarine from the leaves of Macleaya cordata against Ichthyophthirius multifiliis in grass carp (Ctenopharyngodon idella)[J].Parasitology Research,2010,107(5):1035-1042. [17]Yao J Y, Zhou Z M, Li X L, et al. Antiparasitic efficacy of dihydrosanguinarine and dihydrochelerythrine from Macleaya microcarpa against Ichthyophthirius multifiliis in richadsin (Squaliobarbus curriculus)[J].Veterinary Parasitology,2011,183(1/2):8-13. [18]Wang G X, Zhou Z, Jiang D X, et al. In vivo anthelmintic activity of five alkaloids from Macleaya microcarpa (Maxim) Fedde against Dactylogyrus intermedius in Carassius auratus[J]. Veterinary Parasitology,2010,171(3/4):305-313 [19]Wen J H, Wang Y L, Liu Y H, et al. Efficacy of two compounds from Cynanchum paniculatum against Ichthyophthirius multifiliis [J]. Parasitology,2016,12(5):232-239. [20]Schmahl G, Schmidt H, Ritter G. The control of ichthyophthiriasis by a medicated food containing quinine:efficacy tests and ultrastructure investigations[J]. Parasitology Research,1996,82(8):697-705. [21]Lemasters J J, Qian T, Bradham C A, et al. Mitochondrial dysfunction in the pathogenesis of necrotic and apoptotic cell death[J].Journal of Bioenergetics and Biomembranes,1999,31(4):305-319. [22]Vrba J, Dolezel P, Vicar J, et al. Cytotoxic activity of sanguinarine and dihydrosanguinarine in human promyelocytic leukemia HL-60 cells[J].Toxicology in Vitro,2009,23(4):580-588. [23]芦程.血根碱杀灭指环虫机制及对金鱼免疫毒理研究[D].杨陵:西北农林科技大学,2013.
2021, Vol. 40 
