A novel palladium complex with a coumarin-thiosemicarbazone hybrid ligand inhibits Trypanosoma cruzi release from host cells and lowers the parasitemia in vivo.

Autor: Rostán S; Graduate Program in Chemistry, Facultad de Química, Universidad de La República, Montevideo, Uruguay.; Área Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de La República, Montevideo, Uruguay., Porto S; Laboratorio de Inmunorregulación y Enfermedades Infecciosas (LIDIN), Universidade Federal de Minas Gerais, Belo Horizonte, Brasil., Barbosa CLN; Laboratorio de Inmunorregulación y Enfermedades Infecciosas (LIDIN), Universidade Federal de Minas Gerais, Belo Horizonte, Brasil., Assis D; Laboratorio de Inmunorregulación y Enfermedades Infecciosas (LIDIN), Universidade Federal de Minas Gerais, Belo Horizonte, Brasil., Alvarez N; Área Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de La República, Montevideo, Uruguay., Machado FS; Laboratorio de Inmunorregulación y Enfermedades Infecciosas (LIDIN), Universidade Federal de Minas Gerais, Belo Horizonte, Brasil., Mahler G; Laboratorio de Química Farmacéutica, Departamento de Química Orgánica, Facultad de Química, Universidad de La República, Montevideo, Uruguay., Otero L; Área Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de La República, Montevideo, Uruguay. luotero@fq.edu.uy.
Jazyk: angličtina
Zdroj: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry [J Biol Inorg Chem] 2023 Dec; Vol. 28 (8), pp. 711-723. Date of Electronic Publication: 2023 Sep 28.
DOI: 10.1007/s00775-023-02020-2
Abstrakt: In this work, two analogous coumarin-thio and semicarbazone hybrid compounds were prepared and evaluated as a potential antichagasic agents. Furthermore, palladium and platinum complexes with the thiosemicarbazone derivative as ligand (L1) were obtained in order to establish the effect of metal complexation on the antiparasitic activity. All compounds were fully characterized both in solution and in solid state including the resolution of the crystal structure of the palladium complex by X-ray diffraction methods. Unexpectedly, all experimental and theoretical characterizations in the solid state, demonstrated that the obtained palladium and platinum complexes are structurally different: [PdCl(L1)] and [PtCl 2 (HL1)]. All the studied compounds lower the proliferation of the amastigote form of Trypanosoma cruzi while some of them also have an effect on the trypomastigote stage. Additionally, the compounds inhibit T. cruzi release from host cells in variable extents. The Pd compound presented a remarkable profile in all the in vitro experiments, and it showed no toxicity for mammalian cells in the assayed concentrations. In this sense, in vivo experiments were performed for this compound using an acute model of Chagas disease. Results showed that the complex significantly lowered the parasite count in the mice blood with no significant toxicity.
(© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)
Databáze: MEDLINE
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