Visceral leishmaniasis (VL) is a chronic and systemic disease; if untreated, it can cause death in a large number of cases. The therapy is based on the use of antimonials, which have been used for over 50 years. However, cases of resistance have been reported in some countries. In this context, miltefosine (MIL) was introduced to treat antimonial unresponsive cases. Nonetheless, in recent years MIL unresponsive and relapse cases of VL have increasingly been reported. In the current study, the therapeutic potential of compound 5-(4-(3-methanesulfonatepropyl)-1H-1,2,3-triazol-1-yl)dodecyl methanesulfonate (C11), an MIL derivative, was assessed in an experimental VL hamster model. For this purpose, golden hamsters (Mesocricetus auratus) were infected with Leishmania (L.) infantum chagasi and treated daily for 10 days with C11 and MIL administered orally; in addition, Glucantime (GLU), peritoneal route, were administered at 15, 10, 50 mg/kg body weight/day, respectively. Twenty four hours after the end of treatment the animals were euthanatized; and the specimens were collected to evaluate the relative mRNA expression of cytokines IFN-γ, TNF-α, IL-17, TGF-β, IL-4 and IL-10 in fragments of the spleen and liver; moreover, the parasitism in these organs was evaluated as well as the main histopathological alterations. The C11-treated animals showed greater expression of IL-17 and TNF-α cytokines and reduced expression of IL-10 in the spleen in comparison to the infected untreated group (UTG) (p <0.05). The C11 and GLU groups showed a significant reduction in the IgG levels in comparison to the UTG group (p <0.05). Moreover, the C11-treated animals had fewer parasites in the spleen than the UTG animals (reduction of 95.9%), as well as a greater preservation of white pulp architecture in the spleen than the UTG, GLU and MIL groups (p <0.05). For the liver, the animals from the C11 and MIL groups showed a significant increase in TNF-α relative expression in comparison to the UTG animals, which would explain the increase in the number of granulomas and the reduction in the parasitic load (p <0.05). Combined, these findings indicate that C11 is an interesting compound that should be considered for the development of new drugs against VL, mainly due to its leishmanicidal effect and immunostimulating action.

内脏利什曼病（VL）是一种慢性和全身性疾病；如果不及时治疗，可能会导致死亡。该疗法基于使用了50多年的锑。但是，一些国家已经报告了抵抗病例。在这种情况下，引入了miltefosine（MIL）治疗对抗生素无反应的病例。但是，近年来，越来越多地报道了MIL无反应和VL复发的病例。在当前的研究中，化合物MIL（M11衍生物）的化合物5-（4-（3-（甲基甲磺酸丙基））-1 H -1,2,3-三唑-1-基）十二烷基甲磺酸酯（C11）的治疗潜力得到了评估。实验性VL仓鼠模型。为此，金仓鼠（Mesocricetus auratus）被感染利什曼原虫（L.）infantum chagasi每天口服C11和MIL治疗10天；此外，腹膜途径葡聚糖（GLU）的给药剂量分别为15、10、50 mg / kg体重/天。治疗结束后二十四小时，对动物实施安乐死。收集标本，评估脾脏和肝组织中细胞因子IFN-γ，TNF-α，IL-17，TGF-β，IL-4和IL-10的相对mRNA表达。此外，评估了这些器官中的寄生虫病以及主要的组织病理学改变。与经感染的未治疗组（UTG）相比，经C11处理的动物脾脏中IL-17和TNF-α细胞因子的表达更高，而IL-10的表达降低（p <0.05）。与UTG组相比，C11和GLU组的IgG水平显着降低（p <0.05）。此外，与UTG动物相比，经C11处理的动物脾脏中的寄生虫更少（减少了95.9％），并且与UTG，GLU和MIL组相比，脾脏中的白髓结构保留得更好（p <0.05）。对于肝脏，与UTG动物相比，C11和MIL组的动物的TNF-α相对表达显着增加，这可以解释肉芽肿数量的增加和寄生虫负荷的减少（p <0.05 ）。综上所述，这些发现表明，C11是一种有趣的化合物，对于开发针对VL的新药应予以考虑，主要是因为其具有杀菌作用和免疫刺激作用。与UTG，GLU和MIL组相比，脾脏中白髓结构的保存更好（p <0.05）。对于肝脏，与UTG动物相比，C11和MIL组的动物的TNF-α相对表达显着增加，这可以解释肉芽肿数量的增加和寄生虫负荷的减少（p <0.05 ）。综上所述，这些发现表明，C11是一种有趣的化合物，对于开发针对VL的新药应予以考虑，主要是因为其具有杀菌作用和免疫刺激作用。与UTG，GLU和MIL组相比，脾脏中白髓结构的保存更好（p <0.05）。对于肝脏，与UTG动物相比，C11和MIL组的动物的TNF-α相对表达显着增加，这可以解释肉芽肿数量的增加和寄生虫负荷的减少（p <0.05 ）。综上所述，这些发现表明，C11是一种有趣的化合物，对于开发针对VL的新药应予以考虑，主要是因为其具有杀菌作用和免疫刺激作用。这可以解释肉芽肿数量的增加和寄生虫负荷的减少（p <0.05）。综上所述，这些发现表明，C11是一种有趣的化合物，对于开发针对VL的新药应予以考虑，主要是因为其具有杀菌作用和免疫刺激作用。这可以解释肉芽肿数量的增加和寄生虫负荷的减少（p <0.05）。综上所述，这些发现表明，C11是一种有趣的化合物，对于开发针对VL的新药应予以考虑，主要是因为其具有杀菌作用和免疫刺激作用。