Vique-Sánchez José L, Jiménez-Pineda Albertana, Benítez-Cardoza Claudia G
Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, Mexicali, Baja California, México.
Laboratorio de Investigación Bioquímica, ENMyH-Instituto Politécnico Nacional, Ciudad de México, México.
Arch Pharm (Weinheim). 2021 Feb;354(2):e2000263. doi: 10.1002/ardp.202000263. Epub 2020 Oct 5.
Entamoeba histolytica is a cosmopolitan protozoan parasite that can produce infections in the intestine and some organs (liver, lungs, and brain), with worldwide prevalence. There are treatments against E. histolytica (antiparasitics), but as the drugs used in these treatments have presented some type of resistance and/or side effects, there are cases with complications of this disease. Therefore, it is necessary to develop new drugs aimed at a specific therapeutic target against this parasite. Here, we used the compound 5,5'-[(4-nitrophenyl)methylene]bis(6-hydroxy-2-mercapto-3-methyl-4(3H)-pyrimidinone) in the patenting process (called D4). D4 has a reported specific use against a glycolytic enzyme, the triosephosphate isomerase of Trichomonas vaginalis (TvTIM). We determined that D4 has an amoebicidal effect in in vitro cultures, with an IC value of 18.5 µM, and we proposed a specific site of interaction (Lys77, His110, Gln115, and Glu118) in the triosephosphate isomerase of E. histolytica (EhTIM). Furthermore, compound D4 has favorable experimental and theoretical toxicity results. Therefore, D4 should be further investigated as a potential drug against E. histolytica.
溶组织内阿米巴是一种世界性的原生动物寄生虫，可在肠道和一些器官（肝脏、肺和脑）引发感染，在全球范围内广泛存在。针对溶组织内阿米巴有相应的治疗方法（抗寄生虫药物），但由于这些治疗中使用的药物出现了某种类型的耐药性和/或副作用，存在该疾病的并发症病例。因此，有必要开发针对这种寄生虫特定治疗靶点的新药。在此，我们在专利申请过程中使用了化合物5,5'-[(4-硝基苯基)亚甲基]双(6-羟基-2-巯基-3-甲基-4(3H)-嘧啶酮)（称为D4）。据报道D4对一种糖酵解酶——阴道毛滴虫的磷酸丙糖异构酶（TvTIM）有特定作用。我们确定D4在体外培养中有杀阿米巴作用，IC值为18.5 μM，并且我们提出了其在溶组织内阿米巴磷酸丙糖异构酶（EhTIM）中的一个特定相互作用位点（赖氨酸77、组氨酸110、谷氨酰胺115和谷氨酸118）。此外，化合物D4有良好的实验和理论毒性结果。因此，D4应作为一种抗溶组织内阿米巴的潜在药物进一步研究。
