Chagas´ disease continues to be a challenging and neglected public health problem
in many American countries. The etiologic agent, Trypanosoma cruzi, develops intracellularly
in the mammalian host, which hinders treatment efficacy. Progress in the knowledge of parasite
biology and host-pathogen interaction has not been paralleled by the development of
novel, safe and effective therapeutic options. It is then urgent to seek for novel therapeutic
candidates and to implement drug discovery strategies that may accelerate the discovery process.
The most appealing targets for pharmacological intervention are those essential for the
pathogen and, whenever possible, absent or significantly different from the host homolog. The
thiol-polyamine metabolism of T. cruzi offers interesting candidates for a rational design of
selective drugs. In this respect, here we critically review the state of the art of the thiolpolyamine
metabolism of T. cruzi and the pharmacological potential of its components. On
the other hand, drug repurposing emerged as a valid strategy to identify new biological activities
for drugs in clinical use, while significantly shortening the long time and high cost associated
with de novo drug discovery approaches. Thus, we also discuss the different drug repurposing
strategies available with a special emphasis in their applications to the identification of
drug candidates targeting essential components of the thiol-polyamine metabolism of T. cruzi.
Keywords: Therapy, trypanothione, spermidine, polyamines, Chagas´ disease, bioinformatics, screening, approved
drugs, drug repositioning, drug repurposing.
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