Fexinidazole interferes with the growth and structural organization of Trypanosoma cruzi

Fexinidazole (FEX) is a heterocyclic compound and constitutes the first 100% oral treatment drug for African trypanosomiasis. Its effectiveness against Trypanosoma brucei encouraged the investigation of its antiparasitic potential against T. cruzi, the aetiological agent of Chagas disease. Although previous studies addressed the antitrypanosomal effects of FEX, none used electron microscopy to identify the main target structures of T. brucei or T. cruzi. In this work, we used microscopy techniques to analyze the ultrastructural alterations caused by FEX in different developmental stages of T. cruzi. In addition to inhibiting T. cruzi proliferation, with IC50 of 1 mu M for intracellular amastigotes, FEX promoted massive disorganization of reservosomes, the detachment of the plasma membrane, unpacking of nuclear heterochromatin, mitochondrial swelling, Golgi disruption and alterations in the kinetoplast-mitochondrion complex. Together, these observations point to FEX as a potential drug leader for further developing of chemotherapy against Chagas disease.

Automated summary

Fexinidazole has been found to have potential against Trypanosoma cruzi, the causative agent of Chagas disease. It can inhibit parasite proliferation and cause significant alterations in cellular structures.