Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanosomatídeos, Rio de Janeiro, Brasil.
J Antimicrob Chemother. 2012 Jan;67(1):182-90. doi: 10.1093/jac/dkr409. Epub 2011 Oct 10.
Researchers have recently investigated the biological activities of mesoionic (MI) compounds, which have shown in vitro activity against many species of Leishmania, as well as Trypanosoma cruzi. The main goal of this study was to evaluate and compare the activity of three MI compounds against Leishmania amazonensis and Leishmania infantum infection in vivo.
The experiments were carried out using BALB/c mice infected with L. amazonensis or L. infantum as a highly sensitive murine model. The infected mice were treated with MI-HH, MI-4-OCH(3), MI-4-NO(2) or meglumine antimoniate by different routes (intralesional, topical or intraperitoneal).
Treatment with MI-4-OCH(3) and MI-4-NO(2) efficiently contained the progression of cutaneous and visceral leishmaniasis in comparison with the control group or mice treated with meglumine antimoniate. Interestingly, these MI compounds did not produce toxicological effects after treatment. Furthermore, treatment with these compounds led to a modulation of the immune response that was correlated with disease control. In this study, MI compounds, and MI-4-NO(2) in particular, exhibited high activity in the L. infantum murine model. In the L. amazonensis model, intralesional treatment with MI-4-OCH(3) or MI-4-NO(2) showed greater therapeutic efficacy than treatment with meglumine antimoniate, and the new topical formulations of these compounds also displayed great activity in the cutaneous leishmaniasis model.
Upon comparison of each MI compound, MI-4-NO(2) was clearly the compound with the greatest activity in these two in vivo infection models by each administration route tested.
研究人员最近研究了中氮杂环化合物（MI）的生物活性，这些化合物在体外对许多利什曼原虫和克氏锥虫均表现出活性。本研究的主要目的是评估和比较三种 MI 化合物对体内感染亚马逊利什曼原虫和婴儿利什曼原虫的活性。
实验采用 BALB/c 小鼠感染亚马逊利什曼原虫或婴儿利什曼原虫作为高度敏感的小鼠模型。用 MI-HH、MI-4-OCH(3)、MI-4-NO(2)或葡甲胺锑酸盐通过不同途径（瘤内、局部或腹腔内）对感染的小鼠进行治疗。
与对照组或用葡甲胺锑酸盐治疗的小鼠相比，MI-4-OCH(3)和 MI-4-NO(2)治疗能有效控制皮肤利什曼病和内脏利什曼病的进展。有趣的是，这些 MI 化合物在治疗后没有产生毒理学效应。此外，这些化合物的治疗导致免疫反应的调节与疾病控制相关。在本研究中，MI 化合物，特别是 MI-4-NO(2)，在婴儿利什曼原虫小鼠模型中表现出很高的活性。在亚马逊利什曼原虫模型中，MI-4-OCH(3)或 MI-4-NO(2)的瘤内治疗比用葡甲胺锑酸盐治疗显示出更高的治疗效果，这些化合物的新局部制剂在皮肤利什曼病模型中也显示出很强的活性。
在比较每种 MI 化合物时，MI-4-NO(2)显然是通过每种给药途径测试的这两种体内感染模型中活性最强的化合物。
