Trypanosoma cruzi
is a parasite that causes
Chagas disease, which affects millions of individuals in endemic areas of Latin America. One hundred years after the discovery of Chagas disease,
it is still considered a neglected illness because the available drugs are unsatisfactory. Aromatic compounds represent an important class of DNA
minor groove-binding ligands that exhibit potent antimicrobial activity. This study focused on the in vitro activity of 10 aromatic dicationic
compounds against bloodstream trypomastigotes and intracellular forms of
T. cruzi. Our data demonstrated that these compounds display trypanocidal
effects against both forms of the parasite and that seven out of the 10 compounds presented higher anti-parasitic activity against intracellular
parasites compared with the bloodstream forms. Additional assays to determine the potential toxicity to mammalian cells showed that
the majority of the dicationic compounds did not considerably decrease cellular viability. Fluorescent microscopy analysis demonstrated
that although all compounds were localised to a greater extent within the kinetoplast than the nucleus, no correlation could be found between
compound activity and kDNA accumulation. The present results stimulate further investigations of this class of compounds for the rational design
of new chemotherapeutic agents for Chagas disease.
