Análises dos efeitos antiparasitários de complexos metálicos a base de rutênio contra Toxoplasma gondii em células trofoblásticas vilosas humanas

Abstract

Congenital toxoplasmosis is a zoonotic disease with a broad global impact, especially affecting populations in situations of socioeconomic vulnerability and with limited access to quality healthcare services. The adverse effects and the inability of current therapies to achieve definitive cure highlight the need for the development of new therapeutic approaches. This study aimed to evaluate, for the first time, the therapeutic potential of two novel ruthenium(II)-based complexes (Ru-fluorophenoxy and Ru-methylphenyl) against Toxoplasma gondii in a congenital context. Ru-fluorophenoxy and Ru-methylphenyl exhibited promising antiproliferative activity, outperforming their non-coordinated ligands and precursor complex, with IC₅₀ values of 4.12 ± 0.59 and 7.0 ± 0.18 µM, respectively. Furthermore, they exhibited variable cytotoxicity, with CC50 values higher than 100 µM for Ru-fluorophenoxy and 14 ± 1.45 µM for Ru-methylphenyl. Ru-fluorophenoxy was selected for further analyses due to its higher selectivity (SI > 24.27). The three selected concentrations (1.5, 3, and 6 µM) of Ru-fluorophenoxy showed predominant effects during the late stages of infection. In addition, Ru-fluorophenoxy demonstrated an irreversible effect at 6 µM, whereas the 3 µM concentration showed a tendency to reverse the reduction, and the 1.5 µM concentration completely reversed the reduction in proliferation. Interestingly, 6 µM of the compound reduced the parasite’s ability to invade new host cells, an effect that was not observed during the first cycle of infection. Thus, this study demonstrated significant antiparasitic effects of Ruthenium(II) metal complexes against Toxoplasma gondii in congenital toxoplasmosis.