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苯取代的呋喃脒DB569类似物对克氏锥虫体内感染的杀锥虫活性。

Trypanocidal activity of the phenyl-substituted analogue of furamidine DB569 against Trypanosoma cruzi infection in vivo.

作者信息

de Souza Elen M, Oliveira Gabriel M, Boykin David W, Kumar Arvind, Hu Qiyue, De Nazaré C Soeiro Maria

机构信息

Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz FIOCRUZ, Rio de Janeiro, RJ, Brasil.

出版信息

J Antimicrob Chemother. 2006 Sep;58(3):610-4. doi: 10.1093/jac/dkl259. Epub 2006 Jul 19.

Abstract

OBJECTIVES

Aromatic diamidines have been successfully used to combat a wide range of parasites that cause important human infections. One such compound is furamidine (DB75) and we recently reported that one of its analogues, an N-phenyl analogue (DB569), exhibits higher trypanocidal dose and time-dependent effects against different forms of Trypanosoma cruzi as compared with DB75. Our present aim was to investigate the efficacy of DB569 in a T. cruzi mouse model.

METHODS

The trypanocidal activity of the compound was evaluated by clinical, parasitological, histopathological and biochemical investigations.

RESULTS

Treatment with DB569 significantly reduced cardiac parasitism, partially increased the survival rates of mice and lowered the levels of alanine aminotransferase and creatinine indicating a protective role against renal and hepatic lesions caused by the parasite infection.

CONCLUSIONS

Altogether, the data support the potential effect of this class of compounds against T. cruzi and motivate the screening of new diamidines for efficacy against Chagas' disease.

摘要

目的

芳香二脒已成功用于对抗多种导致重要人类感染的寄生虫。其中一种化合物是呋喃脒(DB75),我们最近报道其一种类似物,即N-苯基类似物(DB569),与DB75相比,对不同形态的克氏锥虫表现出更高的杀锥虫剂量和时间依赖性效应。我们目前的目的是在克氏锥虫小鼠模型中研究DB569的疗效。

方法

通过临床、寄生虫学、组织病理学和生化研究评估该化合物的杀锥虫活性。

结果

用DB569治疗可显著降低心脏寄生虫感染,部分提高小鼠存活率,并降低丙氨酸转氨酶和肌酐水平,表明对寄生虫感染引起的肾和肝损伤具有保护作用。

结论

总体而言,这些数据支持这类化合物对克氏锥虫的潜在作用,并促使筛选新的二脒以评估其对恰加斯病的疗效。

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