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首页> 外文期刊>Parasitology >Repurposing strategies for Chagas disease therapy: the effect of imatinib and derivatives against Trypanosoma cruzi
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Repurposing strategies for Chagas disease therapy: the effect of imatinib and derivatives against Trypanosoma cruzi

机译：抗噬菌体疾病治疗的策略：伊马替尼对胰蛋白酶瘤Cruzi的影响

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摘要

Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
机译：Chagas疾病（CD）是由锥虫瘤克鲁齐引起的美洲的忽视寄生病情。患者呈现急性期可能与症状，其次是终身慢性阶段，大多是不确定的，或用心脏和/或消化渐进病变。 Benznidazole（BZ）和Nifurtimox是唯一用于治疗的药物，但在晚期慢性阶段没有效果，许多寄生虫都是天然抗性的。新的替代疗法需要解决这一严重的公共卫生问题。重新定位和组合代表更快，对被忽视的疾病鼓励的较便宜的试验策略。在T.Cruzi和哺乳动物宿主细胞上，在体外评估伊马替尼（IMB）的酪氨酸激酶抑制剂的效果。与BZ相比，IMB对不同的菌株和寄生虫的形式适度活跃。固定比例的组合IMB + BZ是添加剂。筛选新型14种IMB的衍生物，并且3,2-二氟-2-苯基乙酰胺（3E）是T.Cruzi上的BZ，但选择性指数低。结果证明了表型测定的重要性，促进改善IMB衍生物以达到选择性，并证明在药物筛选中使用重新施用和组合。

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  • 来源
    《Parasitology》 |2019年第8期|共7页
  • 作者

    M. R.Sim?es-Silva; J. S.De Araújo; R. B.Peres; P. B.Da Silva; M. M.Batista; L. D.De Azevedo; M. M.Bastos; M. T.Bahia; N.Boechat; M. N. C.Soeiro;

  • 作者单位

    Laboratório de Biologia Celular do Instituto Oswaldo Cruz Funda??o Oswaldo Cruz;

    Laboratório de Biologia Celular do Instituto Oswaldo Cruz Funda??o Oswaldo Cruz;

    Laboratório de Biologia Celular do Instituto Oswaldo Cruz Funda??o Oswaldo Cruz;

    Laboratório de Biologia Celular do Instituto Oswaldo Cruz Funda??o Oswaldo Cruz;

    Laboratório de Biologia Celular do Instituto Oswaldo Cruz Funda??o Oswaldo Cruz;

    Laboratório de Síntese Organica Instituto de Tecnologia em Fármacos – Farmanguinhos Funda??o;

    Laboratório de Síntese Organica Instituto de Tecnologia em Fármacos – Farmanguinhos Funda??o;

    Laboratório de Doen?as Parasitárias Escola de Medicina &

    Núcleo de Pesquisas em Ciências Biol;

    Laboratório de Síntese Organica Instituto de Tecnologia em Fármacos – Farmanguinhos Funda??o;

    Laboratório de Biologia Celular do Instituto Oswaldo Cruz Funda??o Oswaldo Cruz;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 寄生虫病;
  • 关键词

    Chagas disease; drug repurposing; imatinib; imatinib derivatives; in vitro;

    机译：Chagas病;药物重估;imatinib;imatinib衍生物;体外;

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