Treatment against leishmaniasis presents problems, mainly due to the toxicity of the drugs, high cost, and the emergence of resistant strains. A previous study showed that two vanillin-derived synthetic molecules, 3s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], presented antileishmanial activity against , . , and . species. In the present work, 3s and 3t were evaluated to treat . -infected mice. Molecules were used pure or incorporated into Poloxamer 407-based micelles. In addition, amphotericin B (AmpB) and its liposomal formulation, Ambisome®, were used as control. Animals received the treatment and, one and 30 days after, they were euthanized to evaluate immunological, parasitological, and biochemical parameters. Results showed that the micellar compositions (3s/Mic and 3t/Mic) induced significant reductions in the lesion mean diameter and parasite load in the infected tissue and distinct organs, as well as a specific and significant antileishmanial Th1-type immune response, which was based on significantly higher levels of IFN-γ, IL-12, nitrite, and IgG2a isotype antibodies. Drug controls showed also antileishmanial action; although 3s/Mic and 3t/Mic have presented better and more significant parasitological and immunological data, which were based on significantly higher IFN-γ production and lower parasite burden in treated animals. In addition, significantly lower levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in mice treated with 3s/Mic and 3t/Mic, when compared to the others. In conclusion, results suggest that 3s/Mic and 3t/Mic could be considered as therapeutic candidates to treat against . infection.

中文翻译：

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使用香草醛衍生的合成分子掺入聚合胶束进行治疗可有效对抗亚马逊利什曼原虫引起的感染


利什曼病的治疗存在问题，主要是由于药物毒性、成本高以及耐药菌株的出现。先前的研究表明，两种香草醛衍生的合成分子 3s [4-(2-羟基-3-(4-辛基-1H-1,2,3-三唑-1-基)丙氧基)-3-甲氧基苯甲醛]和3t [4-(3-(4-癸基-1H-1,2,3-三唑-1-基)-2-羟基丙氧基)-3-甲氧基苯甲醛]，表现出抗利什曼原虫活性。 ， 和 。物种。在目前的工作中，评估了 3s 和 3t 的治疗效果。 - 受感染的小鼠。分子可单独使用或掺入基于泊洛沙姆 407 的胶束中。此外，还使用两性霉素 B (AmpB) 及其脂质体制剂 Ambisome® 作为对照。动物接受治疗，1 天和 30 天后，对它们实施安乐死，以评估免疫学、寄生虫学和生化参数。结果表明，胶束组合物（3s/Mic 和 3t/Mic）可显着减少受感染组织和不同器官中的病灶平均直径和寄生虫载量，以及特异性且显着的抗利什曼病 Th1 型免疫反应。基于显着较高水平的 IFN-γ、IL-12、亚硝酸盐和 IgG2a 同型抗体。药物管制也显示出抗利什曼病的作用；尽管 3s/Mic 和 3t/Mic 提供了更好、更重要的寄生虫学和免疫学数据，这些数据基于治疗动物中显着更高的 IFN-γ 产量和更低的寄生虫负担。此外，与其他小鼠相比，接受 3s/Mic 和 3t/Mic 治疗的小鼠的尿素、肌酐、丙氨酸转氨酶和天冬氨酸转氨酶水平显着降低。总之，结果表明 3s/Mic 和 3t/Mic 可被视为治疗 的候选药物。感染。