Semeraro Manuela, Boubaker Ghalia, Scaccaglia Mirco, Imhof Dennis, de Sousa Maria Cristina Ferreira, Hänggeli Kai Pascal Alexander, Löwe Anitha, Genchi Marco, Kramer Laura Helen, Vismarra Alice, Pelosi Giorgio, Bisceglie Franco, Ortega-Mora Luis Miguel, Müller Joachim, Hemphill Andrew
Department of Veterinary Science, University of Parma, Via del Taglio, 10, 43126 Parma, Italy.
Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland.
Biomedicines. 2025 Aug 1;13(8):1879. doi: 10.3390/biomedicines13081879.
: is a globally widespread parasite responsible for toxoplasmosis, a zoonotic disease with significant impact on both human and animal health. The current lack of safe and effective treatments underscores the need for new drugs. Earlier, thiosemicarbazones (TSCs) and their metal complexes have shown promising activities against . This study evaluated a gold (III) complex C3 and its TSC ligand C4 for safety in host immune cells and zebrafish embryos, followed by efficacy assessment in a murine model for chronic toxoplasmosis. : The effects on viability and proliferation of murine splenocytes were determined using Alamar Blue assay and BrdU ELISA, and potential effects of the drugs on zebrafish () embryos were detected through daily light microscopical inspection within the first 96 h of embryo development. The parasite burden in treated versus non-treated mice was measured by quantitative real-time PCR in the brain, eyes and the heart. : Neither compound showed immunosuppressive effects on the host immune cells but displayed dose-dependent toxicity on early zebrafish embryo development, suggesting that these compounds should not be applied in pregnant animals. In the murine model of chronic toxoplasmosis, C4 treatment significantly reduced the parasite load in the heart but not in the brain or eyes, while C3 did not have any impact on the parasite load. : These results highlight the potential of C4 for further exploration but also the limitations of current approaches in effectively reducing parasite burden in vivo.
弓形虫是一种全球广泛传播的寄生虫,可引发弓形虫病,这是一种对人类和动物健康都有重大影响的人畜共患病。目前缺乏安全有效的治疗方法,这凸显了开发新药的必要性。此前,硫代氨基脲(TSCs)及其金属配合物已显示出对弓形虫有良好的活性。本研究评估了金(III)配合物C3及其TSC配体C4在宿主免疫细胞和斑马鱼胚胎中的安全性,随后在慢性弓形虫病小鼠模型中进行疗效评估。通过Alamar Blue检测法和BrdU ELISA测定对小鼠脾细胞活力和增殖的影响,并在胚胎发育的前96小时内通过每日光学显微镜检查检测药物对斑马鱼胚胎的潜在影响。通过定量实时PCR测量治疗组和未治疗组小鼠脑、眼和心脏中的寄生虫负荷。两种化合物均未对宿主免疫细胞表现出免疫抑制作用,但对斑马鱼早期胚胎发育显示出剂量依赖性毒性,这表明这些化合物不应应用于怀孕动物。在慢性弓形虫病小鼠模型中,C4治疗显著降低了心脏中的寄生虫负荷,但对脑或眼没有影响,而C3对寄生虫负荷没有任何影响。这些结果突出了C4进一步探索的潜力,但也凸显了当前方法在有效降低体内寄生虫负荷方面的局限性。