Drug repurposing study targeting enzymes involved in Trypanosoma cruzi metabolism
DOI:
https://doi.org/10.34117/bjdv12n4-013Keywords:
Chagas disease, Trypanosoma cruzi, drug repositioning, computer simulationAbstract
Chagas disease, caused by the protozoan Trypanosoma cruzi, is an important public health problem in Latin America. Considering the greater efficacy during the acute phase and the adverse effects associated with the drugs currently available for the treatment, benznidazole and nifurtimox, drug repurposing represents a promising strategy because it is faster and less costly than the discovery and development of new drugs. This study aimed to perform the in silico screening of drugs already approved for clinical use in humans with potential activity against T. cruzi Dm28 strain. For the in silico search and selection of drugs targeting homologous enzymes involved in the parasite’s energy and lipid metabolism, the databases TDR Targets, TriTrypDB, DrugBank, and Therapeutic Targets were used. A total of 139 and 151 genes encoding enzymes related to energy and lipid metabolism were identified, respectively. Subsequently, the correspondence between the amino acid sequences of these enzymes and homologous drug targets was evaluated (E-value < 1e−10). As a result, 265 drugs associated with energy metabolism and 387 associated with lipid metabolism were identified. Among these, 56 and 42 compounds, respectively, were approved for human use. After excluding those whose trypanocidal activity had already been reported (based on searches in the PUBMED, LILACS, and Google Scholar databases), 15 drugs targeting energy metabolism and 22 targeting lipid metabolism were selected. Therefore, this study identified 37 drugs with potential anti-T. cruzi activity, which should be further evaluated through in vitro and in vivo assays to confirm their efficacy.
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