Fraga Carolina Miguel, da Costa Tatiane Luiza, de Castro Ana Maria, Reynoso-Ducoing Olivia, Ambrosio Javier, Hernández-Campos Alicia, Castillo Rafael, Vinaud Marina Clare
Laboratory of Studies of the Host-parasite Relationship, Tropical Pathology and Public Health Institute, Federal University of Goias, Brazil.
Laboratorio de Biologia del Citoesqueleto, Departamento de Microbiologia y Parasitologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), México, DF 04510, Mexico.
Exp Parasitol. 2017 Jan;172:12-17. doi: 10.1016/j.exppara.2016.11.002. Epub 2016 Nov 21.
Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic benzimidazoles due to a differentiated site of action with similar outcome.
由肥胖带绦虫引起的人类囊尾蚴病并不常见;然而,它是囊尾蚴病研究中一个有用的实验模型。苯并咪唑衍生物是广泛用于抗蠕虫的重要抗蠕虫药物。一种新型化合物6-氯-5-(1-萘氧基)-2-(三氟甲基)-1H-苯并咪唑(RCB20)是一种极性较小且亲脂性更强的苯并咪唑衍生物。本研究的目的是检测RCB20对肥胖带绦虫囊尾蚴体外能量代谢的影响。为此,在暴露于6.5和13μM的RCB20和阿苯达唑亚砜(ABZSO)后,通过分光光度法和高效液相色谱法检测寄生虫产生和分泌/排泄(S/E)的代谢产物。暴露于RCB20和ABZSO两种浓度下的寄生虫未摄取的葡萄糖浓度逐渐增加。在暴露于RCB20的寄生虫中,与三羧酸循环相关的所有有机酸浓度都较高。RCB20和ABZSO之间的结构差异导致寄生虫体内不同的靶点,并更大程度地诱导能量途径,如糖酵解和三羧酸循环。由于作用位点不同但结果相似,RCB20是替代抗蠕虫苯并咪唑的良好候选药物。