Iron(III) complex impacts Toxoplasma gondii growth by inducing parasite membrane alterations

Abstract

Therapies for toxoplasmosis are limited, emphasizing the need for treatment options. The in vitro effect of the mononuclear iron(III) complex [Fe(HL1)Cl₃](HL1 = N-2[(pyridine-2-ylmethyl)amino]ethanol) on LLC-MK2 host cells infected with Toxoplasma gondii was investigated. Complex showed low cytotoxicity to host cells up to 500 µM but inhibited parasite growth with IC 50 values of 12.4 nM and 56.0 nM after 24 h and 48 h, respectively demonstrating selective cytotoxicity toward the parasite. These values indicate that the complex is more potent than sulfadiazine and pyrimethamine, two clinically used anti- Toxoplasma agents. The effect of the complex was irreversible after 48 h of treatment and compound withdrawal. Treated infected cells displayed fewer parasites with a rounded morphology. Ultrastructural analysis revealed severe damage of the parasite, including membrane blebbing, cytoplasmic clefts, and rupture of membranes. Biophysical studies demonstrated that the complex caused membrane disruption in parasite-mimicking membranes while increasing order in mammalian-like membranes. These findings suggest that the complex induces membrane alterations in the parasite and displays potent antiparasitic activity at nanomolar concentrations.