Treatment for Chagas disease, a parasitosis caused by Trypanosoma cruzi, has always been based on two drugs, nifurtimox and benznidazole, despite the toxic side effects described after prolonged prescription. In this work, we study a new prospective antitrypanosomal drug based on vanadium, here named V^IVO(5Brsal)(aminophen). We found a good IC₅₀ value, (3.76 ± 0.08) μM, on CL Brener epimastigotes. The analysis of cell death mechanism allowed us to rule out the implication of a mechanism based on early apoptosis or necrosis. Recovery assays revealed a trypanostatic effect, accompanied by cell shape and motility alterations. An uptake mostly associated with the insoluble fraction of the parasites was deduced through vanadium determinations. Concordantly, no drastic changes of the parasite transcriptome were detected after 6 h of treatment. Instead, proteomic analysis uncovered the modulation of proteins involved in different processes such as energy and redox metabolism, transport systems, detoxifying pathways, ribosomal protein synthesis, and proteasome protein degradation. Overall, the results here presented lead us to propose that V^IVO(5Brsal)(aminophen) exerts a trypanostatic effect on T. cruzi affecting parasite insoluble proteins.

中文翻译：

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利用高通量方法阐明新型钒基化合物对克氏锥虫的作用机理。

尽管长期服用处方药后会产生毒性副作用，但治疗南美锥虫病（一种由克氏锥虫引起的寄生虫病）的治疗方法一直以尼呋替莫和苯硝唑这两种药物为基础。在这项工作中，我们研究了一种基于钒的新的预期抗锥虫药物，此处命名为V ^IV O（5Brsal）（aminophen）。我们发现一个好的IC ₅₀值（3.76±0.08）μM，关于CL Brener附子。细胞死亡机制的分析使我们能够排除基于早期凋亡或坏死的机制的含义。回收率测定显示出锥虫作用，并伴有细胞形状和运动性改变。通过钒的测定推导了与寄生虫的不溶部分主要相关的摄取。一致地，治疗6小时后未检测到寄生虫转录组的急剧变化。相反，蛋白质组学分析揭示了涉及不同过程（例如能量和氧化还原代谢，运输系统，解毒途径，核糖体蛋白质合成和蛋白酶体蛋白质降解）的蛋白质调控。总体而言，此处给出的结果使我们提出了V ^IVO（5Brsal）（aminophen）对T. cruzi影响寄生虫不溶蛋白的锥虫作用。