Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 μmol · L ^-1. Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs.

中文翻译：

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杀螨剂及其衍生物对细粒棘球E的作用及DNA损伤靶标的比较。

囊性棘球co病（CE）是一种世界范围的人畜共患病。目前，CE的治疗选择是有限的。临床上用于棘球ech虫病化学疗法的主要药物是阿苯达唑和甲苯达唑，但它们主要基于高剂量发挥长期的抗寄生虫作用。因此，迫切需要有效且安全的抗CE药物。先前的研究已经确定了维他命（HM）作为一种新的抗CE药物。在这项研究中，在体外和体内评估了甜菜碱衍生物的功效。在体外对氨苄基衍生物进行了抗颗粒大肠杆菌（PSC）的测试。香豆素衍生物的作用随时间和浓度的不同而不同，其抗CE作用优于香豆素。死亡率PSC中的100的浓度达到在暴露于去氢衍生物后的第5天100％μ摩尔·L ^-1。与未治疗的模型对照小鼠相比，在用harmine衍生物治疗的感染小鼠中，囊肿的重量显着降低。氨苄基衍生物的效果要比氨苄基更好，氨苄基衍生物与阿苯达唑之间存在显着差异（P <0.001）。对实验小鼠器官（肝，脾，肺，脑和小肠）的组织病理学检查显示，除了肝脏中的轻度炎症外，组织没有任何变化。秀丽隐杆线虫的神经毒性试验表明，该衍生物抑制秀丽隐杆线虫的运动，进食，知觉行为和乙酰胆碱酯酶活性，其作用低于甜菜碱。另外，初步证明了对HM衍生物的干预会引起DNA损伤。这项研究揭示了HM衍生物作为一类新的抗CE药物的潜力，并表明Topo2a可能是抗CE药物开发的有希望的目标。