RT Journal Article
T1 In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts
A1 Semeraro, Manuela
A1 Boubaker, Ghalia
A1 Scaccaglia, Mirco
A1 Imhof, Dennis
A1 de Sousa, Maria Cristina Ferreira
A1 Hänggeli, Kai Pascal Alexander
A1 Löwe, Anitha
A1 Genchi, Marco
A1 Kramer, Laura Helen
A1 Vismarra, Alice
A1 Pelosi, Giorgio
A1 Bisceglie, Franco
A1 Ortega Mora, Luis Miguel
A1 Müller, Joachim
A1 Hemphill, Andrew
AB 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
PB MDPI
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/124769
UL https://hdl.handle.net/20.500.14352/124769
LA eng
NO 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
NO Author Contributions: Conceptualization, M.S. (Manuela Semeraro), G.B., J.M. and A.H.; methodology, M.S. (Manuela Semeraro), G.B., M.S. (Mirco Scaccaglia), D.I., M.C.F.d.S., A.L. and K.P.A.H.; software, M.S. (Manuela Semeraro) and G.B.; validation, M.S. (Manuela Semeraro) and G.B.; formal analysis, M.S. (Manuela Semeraro), G.B., D.I. and A.H.; investigation, M.S. (Manuela Semeraro), G.B. and A.H.; resources, A.H.; data curation, M.S. (Manuela Semeraro) and G.B.; writing—original draft preparation, M.S. (Manuela Semeraro), G.B., J.M., A.H. and L.H.K.; writing—review and editing, M.S. (Manuela Semeraro), M.S. (Mirco Scaccaglia), A.H., G.B., J.M., L.H.K., A.V., M.G., F.B., G.P. and L.M.O.-M.; visualization, M.S. (Manuela Semeraro), G.B. and A.H.; supervision, G.B. and A.H.; project administration, G.B. and A.H.; funding acquisition, A.H. All authors have read and agreed to the published version of the manuscript.
NO Swiss National Science Foundation (Swiss)
NO The Uniscientia Foundation
NO Swiss Government
DS Docta Complutense
RD 12 mar 2026