Liu Congshan, Yin Jianhai, Xue Jian, Tao Yi, Hu Wei, Zhang Haobing
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, National Center for International Research on Tropical Diseases, WHO Collaborating Centre for Tropical Diseases, Shanghai 200025, China.
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, National Center for International Research on Tropical Diseases, WHO Collaborating Centre for Tropical Diseases, Shanghai 200025, China; Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Acta Trop. 2018 Jun;182:285-290. doi: 10.1016/j.actatropica.2017.08.031. Epub 2017 Aug 30.
Cystic echinococcosis is a globally distributed zoonotic disease, which is caused by the larval stage of Echinococcosus granulosus sensu lato. The chemotherapy of the disease is limited to the use of benzimidazoles. Recently, mefloquine and its analogues, aminoalcohol-carbazole, and some amino alcohol derivatives were reported to display inhibitory effects on parasites. Here, the activities of 130 amino alcohol compounds against E. granulosus were tested on protoscoleces and germinal cells at a concentration of 20 μg/ml over a period of three days. As a result, sixteen compounds totally were effective against both protoscoleces and germinal cells, and their IC and LC were also calculated respectively. Then effects of the most active compounds were observed on metacestodes over 14 days in vitro. Although the structure of active compounds were variable, hydroxyl and amino groups connected by two carbon atoms are held in common as the key feature of these compounds. The further investigation on metacestodes incubated with these active compounds revealed that the effects of JF16 and BTB4 were comparable to that of mefloquine and mebendazole. In addition, the ultrastructure alternations induced by these compounds on E. granulosus were confirmed by scanning electron microscopy and transmission electron microscopy observations. In conclusion, amino alcohols were a class of compounds with efficacy against E. granulosus. The most effective compounds JF16 and BTB4 indicated that their basic structure would be useful in the synthesis of new compound for the treatment of echinococcosis. However, their in vivo efficacy and toxicity need to be carefully evaluated in the future.
囊性棘球蚴病是一种全球分布的人畜共患病，由细粒棘球绦虫复合体的幼虫阶段引起。该疾病的化疗仅限于使用苯并咪唑类药物。最近，有报道称甲氟喹及其类似物、氨基醇咔唑和一些氨基醇衍生物对寄生虫有抑制作用。在此，以20μg/ml的浓度在原头节和生发细胞上对130种氨基醇化合物针对细粒棘球绦虫进行了为期三天的活性测试。结果，共有16种化合物对原头节和生发细胞均有效，并且还分别计算了它们的半数抑制浓度（IC）和半数致死浓度（LC）。然后在体外观察了最具活性的化合物对中绦期幼虫14天的影响。尽管活性化合物的结构各不相同，但由两个碳原子连接的羟基和氨基作为这些化合物的关键特征是共同存在的。对用这些活性化合物孵育的中绦期幼虫的进一步研究表明，JF16和BTB4的效果与甲氟喹和甲苯达唑相当。此外，通过扫描电子显微镜和透射电子显微镜观察证实了这些化合物对细粒棘球绦虫诱导的超微结构变化。总之，氨基醇是一类对细粒棘球绦虫有效的化合物。最有效的化合物JF16和BTB4表明它们的基本结构将有助于合成治疗棘球蚴病的新化合物。然而，它们的体内疗效和毒性未来需要仔细评估。
