2026-06-29T02:42:26Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1247692025-10-09T23:55:45Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Semeraro, Manuela author Boubaker, Ghalia author Scaccaglia, Mirco author Imhof, Dennis author de Sousa, Maria Cristina Ferreira author Hänggeli, Kai Pascal Alexander author Löwe, Anitha author Genchi, Marco author Kramer, Laura Helen author Vismarra, Alice author Pelosi, Giorgio author Bisceglie, Franco author Ortega Mora, Luis Miguel author Müller, Joachim author Hemphill, Andrew author 2025 Background: Toxoplasma gondii 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 T. gondii. 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. Methods: 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 (Danio rerio) 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. Results: 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. Conclusions: These results highlight the potential of C4 for further exploration but also the limitations of current approaches in effectively reducing parasite burden in vivo Semeraro, M., Boubaker, G., Scaccaglia, M., Imhof, D., de Sousa, M. C. F., Hänggeli, K. P. A., Löwe, A., Genchi, M., Kramer, L. H., Vismarra, A., Pelosi, G., Bisceglie, F., Ortega-Mora, L. M., Müller, J., & Hemphill, A. (2025). In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts. Biomedicines, 13(8), 1879. https://doi.org/10.3390/biomedicines13081879 10.3390/biomedicines13081879 https://hdl.handle.net/20.500.14352/124769 2227-9059 https://doi.org/10.3390/biomedicines13081879 40868133 In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts