{"title":"Furan derivative affects the cell division and mitochondrial integrity of tachyzoites of Toxoplasma gondii","authors":"Juliana de Araujo Portes , Anushree Achari , Jayaraman Vinayagam , Pinaki Bhattacharjee , Sourav Chatterjee , Parasuraman Jaisankar , Wanderley de Souza","doi":"10.1016/j.exppara.2025.108988","DOIUrl":null,"url":null,"abstract":"<div><div><em>Toxoplasma gondii</em> 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 <em>T. gondii</em>, we have described here the effects of Furan derivatives on <em>T. gondii in vitro</em>. They were previously used with relevant activity against <em>Leishmania amazonensis</em> and <em>Trypanosoma cruzi.</em> The <em>anti-Toxoplasma</em> effects of the furan derivatives were evaluated using tachyzoites of <em>T. gondii</em> 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 <strong>3g</strong>, 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<strong>.</strong> 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 <strong>3g</strong> is a potential candidate for further studies <em>in vivo</em> to find alternative drugs to treat <em>T. gondii</em> infections.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"275 ","pages":"Article 108988"},"PeriodicalIF":1.4000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental parasitology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014489425000931","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PARASITOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.