Toxoplasma gondii apoptosis and cellular division alterations after in vitro treatment with copper(II) complexes

Toxoplasma gondii is the causative agent of toxoplasmosis, which is one of the most common parasitic diseases in the world. Toxoplasmosis causes severe damage to immunocompromised hosts, and the most frequently used therapy is the combination of pyrimethamine and sulfadiazine, which has side effects. Thus, there is a need for new therapies that target T. gondii. Herein, we present the anti-Toxoplasma effect of two new copper(II) complexes: [(H2L1) Cu (μ-Cl)2 Cu(H2L1)] Cl2. 5H2O (1) and [(H2L2) Cu (μ-Cl)2 Cu(H2L2)] Cl2. 6H2O (2). Complexes 1 and 2 irreversibly controlled parasite growth in vitro, with IC50 values of 3.57 μM and 0.78 μM, respectively, after 48 h. These compounds induced part of the tachyzoite population to convert to bradyzoites, which eventually die. The cell death mechanism was unknown, but signs of apoptosis, such as membrane blebs and nuclear fragmentation, and necrosis, such as plasma membrane disruption, intense cytoplasm vesiculation and the release of cellular contents, were seen. In addition, complex (1) interfered with the correct disposition of the inner membrane complex of the parasite, affecting cell division. These results indicate that these copper compounds have potential effects against T. gondii and may be used as drugs in the future or serve as prototypes for the development of new drugs to treat toxoplasmosis.