PARA UMA DOENÇA TÃO ANTIGA, O VISLUMBRE DE NOVOS TRATAMENTOS PROMISSORES NA DOENÇA DE CHAGAS

Sabrina Sehn Hilgert, Sofia Comássio de Paula Lima, Sofia Ferreira Salviano, Cristiane Tefé-Silva
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Abstract

It has been more than 100 years since the discovery of Chagas Disease (CD). However, the repertoire indicated for its treatment is still limited. Thus, this article aims to present a review of the new pharmacological strategies being studied for CD. This literature review, consisting of 68 articles, from 1957 to 2021, was carried out on several scientific platforms. Positive effects from benznidazole have been described in the acute and chronic phases, in addition to its association with itraconazole in the acute phase. Among the cruzain inhibitors, the compound K777 presented trypanocidal effects, although demonstrating major adverse effects, while its analogue WRR-483 demonstrated great beneficial effects in vivo and in vitro. As for the nitroheterocyclics, fexinidazole showed high rates of cure in animal model, in addition to low toxicity. Nifurtimox, in early chronic stages, was able to delay the progression of tissue damage and reduce the parasite load. The compound WC-9, a squalene synthase inhibitor, showed potential inhibition of T. cruzi replication. Regarding aromatic diamidines, many compounds were able to stop the trypanosome, both in vitro and in vivo models. It was concluded that there are favorable findings to improve the treatment of CD. However, the development of effective new drugs does not only depend on their effective action, but also on numerous variables that must be circumvented, such as the reduction of side effects, treatment time and adherence to the current medication of choice, as well as the investment in production and distribution to the population.
对于如此古老的疾病,恰加斯病有希望的新治疗方法的曙光
恰加斯病(Chagas Disease, CD)的发现距今已有100多年。然而,其治疗方法仍然有限。因此,本文旨在综述正在研究的新的CD药理学策略。该文献综述包括68篇文章,从1957年到2021年,在几个科学平台上进行。除了在急性期与伊曲康唑相关外,苯并硝唑在急性期和慢性期均有积极作用。在cruzain抑制剂中,化合物K777虽然表现出主要的副作用,但仍表现出锥虫作用,而其类似物WRR-483在体内和体外均表现出很大的有益作用。对于硝基杂环类化合物,非昔硝唑在动物模型上的治愈率高,毒性低。在早期慢性阶段,硝呋替莫能够延缓组织损伤的进展并减少寄生虫负荷。角鲨烯合成酶抑制剂WC-9对克氏t细胞复制具有潜在的抑制作用。对于芳香族二胺,许多化合物能够在体外和体内模型中阻止锥虫。结论是,有一些有利的发现可以改善乳糜泻的治疗。然而,有效新药的开发不仅取决于它们的有效作用,还取决于许多必须绕过的变量,例如减少副作用,治疗时间和对当前药物选择的依从性,以及生产和向人群分发的投资。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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