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Biomedicines
Volume 13
Issue 8
10.3390/biomedicines13081879
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Article

In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts

by
Manuela Semeraro
1,*,
Ghalia Boubaker
2,
Mirco Scaccaglia
3,
Dennis Imhof
2,
Maria Cristina Ferreira de Sousa
2,
Kai Pascal Alexander Hänggeli
2,
Anitha Löwe
2,
Marco Genchi
1,
Laura Helen Kramer
1,*,
Alice Vismarra
1,
Giorgio Pelosi
3,
Franco Bisceglie
3,
Luis Miguel Ortega-Mora
4,
Joachim Müller
2 and
Andrew Hemphill
2
1
Department of Veterinary Science, University of Parma, Via del Taglio, 10, 43126 Parma, Italy
2
Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland
3
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area Delle Scienze, 11/a, 43124 Parma, Italy
4
SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Biomedicines 2025, 13(8), 1879; https://doi.org/10.3390/biomedicines13081879 (registering DOI)
Submission received: 26 June 2025 / Revised: 29 July 2025 / Accepted: 31 July 2025 / Published: 1 August 2025
(This article belongs to the Section Microbiology in Human Health and Disease)
Versions Notes

Abstract

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.
Keywords: T. gondii; gold-based compounds; thiosemicarbazones; in vivo T. gondii; gold-based compounds; thiosemicarbazones; in vivo

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MDPI and ACS Style

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.; et al. In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts. Biomedicines 2025, 13, 1879. https://doi.org/10.3390/biomedicines13081879

AMA Style

Semeraro M, Boubaker G, Scaccaglia M, Imhof D, de Sousa MCF, Hänggeli KPA, Löwe A, Genchi M, Kramer LH, Vismarra A, et al. In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts. Biomedicines. 2025; 13(8):1879. https://doi.org/10.3390/biomedicines13081879

Chicago/Turabian Style

Semeraro, Manuela, Ghalia Boubaker, Mirco Scaccaglia, Dennis Imhof, Maria Cristina Ferreira de Sousa, Kai Pascal Alexander Hänggeli, Anitha Löwe, Marco Genchi, Laura Helen Kramer, Alice Vismarra, and et al. 2025. "In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts" Biomedicines 13, no. 8: 1879. https://doi.org/10.3390/biomedicines13081879

APA Style

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

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