Anti-Toxoplasma Gondii Effect of Metalocomplex Compounds N0414 and N5814 / Efeito Anti-Toxoplasma Gondii Do Composto Metalocomplexo N0414 E N5814

Abstract

Toxoplasma gondii, toxoplasmosis agent, is a obligate intracellular protozoan that is able of infecting a broad spectrum of vertebrate's cells. Toxoplasmosis is a pathology related to severe damages to immunocompromised hosts and its current chemotherapy is quite restricted, being more used the combination of sulfadiazine and pyrimethamine, which is a therapy associated with adverse reactions. This fact highlights the importance of the study of new drugs against Toxoplasma gondii. Has been studied the biological effect of new metallocomplexe compounds, which are inorganic compounds that present promising biological activity as fungicide, bactericide and antiviral. The metallocomplexes, dinuclear ferric compounds N0414 (Fe alfanaftol BMPA) and N5814 (Fe beta-naphthol BMPA) showed activity against Toxoplasma gondii in vitro and it was nontoxic to LLC-MK2 cells, being able to reduce the activity of crucial antioxidant enzymes for the defense of the parasite. In this project, it will be investigated the activities of compounds of the metallocomplexes family as the compounds coordinated to sulfadiazine as the nucleus compound of ferric N0414 and N5814, which showed anti-Toxoplasma gondii activities and were able to eliminate the infection in almost all host cells. In further steps, we will investigate what kind of death the parasite undergoes after the treatment with the compounds through the ultrastructure analysis and the usage of specific markers by fluorescence microscopy. The compounds will also be used in vivo tests with mouse models in the acute phase of toxoplasmosis to prove the efficacy of these compounds.

In vitro expansion of T. gondii tachyzoites using a magnetic aggregation 3D cell culture

“…The orientation of the tomes does not favor the display of intracellular structures of what are supposed to be tachyzoites, but there is at least one impact reference in the literature showing similar ndings and in the same slice orientation(Ferguson and Dubremetz 2013). Findings in G and H were classi ed as tachyzoites associated with the cytoplasmic membrane of cells in cross-section, correlating the morphology found with other ndings in the literature(Duarte et al 2021;Nishi et al 2021;Liu et al 2021). It was possible to observe the nuclei of the parasites and structures with morphology related to that of the rhoptries.…”