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一种新型有机碲化合物(RT-01)作为一种新型抗利什曼原虫药物。

A novel organotellurium compound (RT-01) as a new antileishmanial agent.

作者信息

Lima Camila Bárbara Cantalupo, Arrais-Silva Wagner Welber, Cunha Rodrigo Luiz Oliveira Rodrigues, Giorgio Selma

机构信息

Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, SP, Brazil.

出版信息

Korean J Parasitol. 2009 Sep;47(3):213-8. doi: 10.3347/kjp.2009.47.3.213. Epub 2009 Aug 28.

Abstract

Leishmaniasis is a neglected disease and endemic in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate the effect of RT-01, an organotellurane compound presenting biological activities, in 2 experimental systems against Leishmania amazonensis. The in vitro system consisted of promastigotes and amastigotes forms of the parasite, and the in vivo system consisted of L. amazonensis infected BALB/c mice, an extremely susceptible mouse strain. The compound proved to be toxic against promastigotes and amastigotes. The study also showed that treatment with RT-01 produces an effect similar to that treatment with the reference antimonial drug, Glucantime, in L. amazonensis infected mice. The best results were obtained following RT-01 intralesional administration (720 microg/kg/day); mice showed significant delay in the development of cutaneous lesions and decreased numbers of parasites obtained from the lesions. Significant differences in tissue pathology consisted mainly of no expressive accumulation of inflammatory cells and well-preserved structures in the skin tissue of RT-01-treated mice compared with expressive infiltration of infected cells replacing the skin tissue in lesions of untreated mice. These findings highlight the fact that the apparent potency of organotellurane compounds, together with their relatively simple structure, may represent a new avenue for the development of novel drugs to combat parasitic diseases.

摘要

利什曼病是一种被忽视的疾病,在发展中国家呈地方性流行。缺乏足够有效的化疗药物来对抗这种感染促使人们对众多化合物展开研究。本研究的目的是在2个实验系统中研究具有生物活性的有机碲化合物RT - 01对亚马逊利什曼原虫的作用。体外系统由该寄生虫的前鞭毛体和无鞭毛体形式组成,体内系统由感染亚马逊利什曼原虫的BALB/c小鼠组成,这是一种极其易感的小鼠品系。该化合物被证明对前鞭毛体和无鞭毛体有毒性。研究还表明,用RT - 01治疗在感染亚马逊利什曼原虫的小鼠中产生的效果与用参考抗锑药物葡甲胺治疗的效果相似。RT - 01病灶内给药(720微克/千克/天)后获得了最佳结果;小鼠皮肤病变的发展明显延迟,且从病变处获得的寄生虫数量减少。组织病理学的显著差异主要在于,与未治疗小鼠病变中感染细胞大量浸润取代皮肤组织相比,RT - 01治疗小鼠的皮肤组织中炎症细胞没有明显积聚且结构保存完好。这些发现凸显了这样一个事实,即有机碲化合物明显的效力及其相对简单的结构,可能为开发抗寄生虫疾病的新型药物提供一条新途径。

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