Furan derivative affects the cell division and mitochondrial integrity of tachyzoites of Toxoplasma gondii

IF 1.4 4区 医学 Q3 PARASITOLOGY
Juliana de Araujo Portes , Anushree Achari , Jayaraman Vinayagam , Pinaki Bhattacharjee , Sourav Chatterjee , Parasuraman Jaisankar , Wanderley de Souza
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Abstract

Toxoplasma gondii is an obligate intracellular protozoan, the causative agent of toxoplasmosis. The current treatment against toxoplasmosis is based on the combination of sulfadiazine and pyrimethamine, which are toxic and unable to clear the infection. Due to the need for new active drugs against T. gondii, we have described here the effects of Furan derivatives on T. gondii in vitro. They were previously used with relevant activity against Leishmania amazonensis and Trypanosoma cruzi. The anti-Toxoplasma effects of the furan derivatives were evaluated using tachyzoites of T. gondii from RH strain and as host cells the human foreskin fibroblast (HFF) and the epithelial lineage from Macaca mulatta LLC-MK2. High-content screening and other microscopy techniques were employed to analyze the infected cells after incubation in the presence of the compounds tested. The most effective derivative was 3g, presenting a 50 % inhibitory concentration (IC50) of 4.3 μM after 48 h of incubation. The 50 % cytotoxic concentration (CC50) in the host cells was 50 μM after a 72-h treatment. The ultrastructural analysis showed that after treatment the parasites presented cytoplasmic emptying, mitochondrial swelling, and interference with cell division. It was revealed by TUNEL assay that the parasites dyed in part due to an apoptosis-like cell death. These findings suggest that the furan derivative 3g is a potential candidate for further studies in vivo to find alternative drugs to treat T. gondii infections.

Abstract Image

呋喃衍生物影响刚地弓形虫速殖子细胞分裂和线粒体完整性
刚地弓形虫是一种专性细胞内原生动物,是弓形虫病的病原体。目前对弓形虫病的治疗是基于磺胺嘧啶和乙胺嘧啶的组合,这是有毒的,不能清除感染。由于需要新的抗弓形虫活性药物,我们在这里描述了呋喃衍生物对弓形虫的体外作用。它们以前用于对亚马逊利什曼原虫和克氏锥虫具有相关活性。以RH株刚地弓形虫速殖子为宿主细胞,人包皮成纤维细胞(HFF)和猕猴LLC-MK2上皮细胞系为宿主细胞,对呋喃衍生物的抗弓形虫作用进行了评价。高含量筛选和其他显微镜技术被用来分析感染细胞在被测试化合物的存在下孵育后。最有效的衍生物是3g,孵育48 h后,IC50为4.3 μM,达到50%的抑制浓度。作用72 h后,宿主细胞50%细胞毒浓度(CC50)为50 μM。超微结构分析显示,处理后的寄生虫细胞质出现排空、线粒体肿胀、细胞分裂受到干扰。TUNEL实验显示,寄生虫染色的部分原因是细胞凋亡样死亡。这些发现表明呋喃衍生物3g是一个潜在的候选者,可以在体内进一步研究寻找治疗弓形虫感染的替代药物。
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来源期刊
Experimental parasitology
Experimental parasitology 医学-寄生虫学
CiteScore
3.10
自引率
4.80%
发文量
160
审稿时长
3 months
期刊介绍: Experimental Parasitology emphasizes modern approaches to parasitology, including molecular biology and immunology. The journal features original research papers on the physiological, metabolic, immunologic, biochemical, nutritional, and chemotherapeutic aspects of parasites and host-parasite relationships.
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