Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av do Café, sn/n, 14040-903 Ribeirão Preto, SP, Brazil.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
Biomed Res Int. 2019 Jul 4;2019:8301569. doi: 10.1155/2019/8301569. eCollection 2019.
Chagas disease is a tropical illness caused by the protozoan . The disease affects populations of the Americas and has been spread to other continents due to the migration process. The disease is partially controlled by two drugs, Benznidazole and Nifurtimox. These molecules are active in the acute phase of the infection but are usually ineffective during the symptomatic chronic phase. Several research groups have developed novel candidates to control Chagas disease; however, no novel commercial formulation is available. In this article, we described the anti- effects of phenothiazinium dyes in amastigote and trypomastigote forms of the parasite. Methylene Blue, New Methylene Blue, Toluidine Blue O, and 1,9-Dimethyl Methylene Blue inhibited the parasite proliferation at nanomolar concentrations and also demonstrated low toxicity in host cells. Moreover, combinations of phenothiazinium dyes indicated a synergic pattern against amastigotes compared to the Benznidazole counterparts. Phenothiazinium dyes levels of reactive oxygen species (ROS) and decreased the mitochondrial potential in trypomastigotes, indicating the mechanism of action of the dyes in . Our article offers a basis for future strategies for the control of Chagas disease using low-cost formulations, an important point for endemic underdeveloped regions.
恰加斯病是一种由原生动物引起的热带疾病。该疾病影响美洲的人群，并由于迁移过程已传播到其他大洲。两种药物，苯并咪唑和硝呋替莫，部分控制了这种疾病。这些分子在感染的急性期有效，但在有症状的慢性期通常无效。几个研究小组已经开发出了控制恰加斯病的新候选药物；然而，没有新的商业制剂可用。在本文中，我们描述了吩噻嗪染料对寄生虫的无鞭毛体和鞭毛体形式的抗效应。亚甲蓝、新亚甲蓝、甲苯胺蓝 O 和 1,9-二甲基亚甲蓝在纳摩尔浓度下抑制寄生虫增殖，并且在宿主细胞中也显示出低毒性。此外，与苯并咪唑对照物相比，吩噻嗪染料对无鞭毛体的组合表现出协同模式。吩噻嗪染料增加了活性氧物种（ROS）的水平并降低了鞭毛体的线粒体电势，表明染料在寄生虫中的作用机制。我们的文章为使用低成本制剂控制恰加斯病的未来策略提供了基础，这对于欠发达的流行地区非常重要。
