Roquini Daniel B, Silva Gabriel L, Ferreira Leonardo L G, Andricopulo Adriano D, Wilairatana Polrat, De Moraes Josué
Center for Neglected Diseases Research, Guarulhos University, Guarulhos, Brazil.
Laboratory of Medicinal and Computational Chemistry, Center for Research and Innovation in Biodiversity and Drug Discovery, Physics Institute of Sao Carlos, University of São Paulo, São Carlos, Brazil.
Front Pharmacol. 2022 Jun 21;13:901459. doi: 10.3389/fphar.2022.901459. eCollection 2022.
Human helminthiasis affects approximately one in five people in the world and disproportionally affects the poorest and most deprived communities. Human angiostrongyliasis, caused by nematode , is a neglected emerging disease with escalating importance worldwide. Chemotherapy is the main control method for helminthiasis, but the therapeutic arsenal is limited. This study aimed to evaluate the antiparasitic and molecular properties of the major available anthelmintic drugs against . The first-stage larvae (L1), isolated from feces of an -infected rat, were exposed to a set of 12 anthelmintic drugs . The larvae were monitored, and the concentration- and time-dependent viability alterations were determined. From 12 anthelmintic drugs, six (ivermectin, salamectin, moxidectin, pyrantel pamoate, albendazole and levamisole) were identified to affect the viability of . The macrocyclic lactones (ivermectin, salamectin, moxidectin) and the imidazothiazole levamisole, were the most effective drugs, with IC ranging from 2.2 to 2.9 µM and a rapid onset of action. Albendazole, the most widely used anthelmintic in humans, had a slower onset of action, but an IC of 11.3 µM was achieved within 24 h. Molecular properties studies suggest that a less lipophilic character and low molecular weight could be favorable for the biological activity of the non-macrocyclic molecules. Collectively, our study revealed that macrocyclic lactones, levamisole, pyrantel pamoate, and albendazole are important anthelmintic agents against . The results of this study also suggest that L1 may be a particularly sensitive and useful model for anthelmintic studies.
人体蠕虫感染影响着世界上约五分之一的人口,且对最贫困和最弱势群体的影响尤为严重。由线虫引起的人体广州管圆线虫病是一种被忽视的新发疾病,在全球范围内的重要性日益增加。化疗是蠕虫感染的主要控制方法,但治疗药物有限。本研究旨在评估主要现有驱虫药物对[病原体名称未明确给出]的抗寄生虫和分子特性。从感染[病原体名称未明确给出]的大鼠粪便中分离出的第一期幼虫(L1),暴露于一组12种驱虫药物中。对幼虫进行监测,并确定浓度和时间依赖性的活力变化。在12种驱虫药物中,有六种(伊维菌素、赛拉菌素、莫西菌素、吡喹酮、阿苯达唑和左旋咪唑)被确定会影响[病原体名称未明确给出]的活力。大环内酯类药物(伊维菌素、赛拉菌素、莫西菌素)和咪唑噻唑类的左旋咪唑是最有效的药物,IC50范围为2.2至2.9μM,且起效迅速。阿苯达唑是人类使用最广泛的驱虫药,起效较慢,但在24小时内达到了11.3μM的IC50。分子特性研究表明,亲脂性较低和分子量较小可能有利于非大环分子的生物活性。总体而言,我们的研究表明大环内酯类药物、左旋咪唑、吡喹酮和阿苯达唑是对抗[病原体名称未明确给出]的重要驱虫剂。本研究结果还表明,L1幼虫可能是驱虫研究中特别敏感且有用的模型。