In silico search of energy metabolism inhibitors for alternative leishmaniasis treatments.
Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genus Leishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways of Leishmania include several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes in Leishmania could be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93 Leishmania energy metabolism targets. Using each gene's designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis.
Federal Institute of Education, Science and Technology of Goiânia, 76300000 Ceres, GO, Brazil ; Goiás Network of Research in Biotechnology and Metabolomics of the Host-Parasite Relationship, Goiás Research Support Foundation (FAPEG), 74605050 Goiânia, GO, Brazil.
Lourival A
LA
Silva
Goiás Network of Research in Biotechnology and Metabolomics of the Host-Parasite Relationship, Goiás Research Support Foundation (FAPEG), 74605050 Goiânia, GO, Brazil ; Institute of Tropical Pathology and Public Health, Federal University of Goiás, 74605050 Goiânia, GO, Brazil.
Marina C
MC
Vinaud
Federal Institute of Education, Science and Technology of Goiânia, 76300000 Ceres, GO, Brazil ; Institute of Tropical Pathology and Public Health, Federal University of Goiás, 74605050 Goiânia, GO, Brazil.
Ana Maria
0000-0003-3327-967X
AM
Castro
Goiás Network of Research in Biotechnology and Metabolomics of the Host-Parasite Relationship, Goiás Research Support Foundation (FAPEG), 74605050 Goiânia, GO, Brazil ; Institute of Tropical Pathology and Public Health, Federal University of Goiás, 74605050 Goiânia, GO, Brazil.
Pedro Vítor L
PV
Cravo
Goiás Network of Research in Biotechnology and Metabolomics of the Host-Parasite Relationship, Goiás Research Support Foundation (FAPEG), 74605050 Goiânia, GO, Brazil ; Institute of Tropical Pathology and Public Health, Federal University of Goiás, 74605050 Goiânia, GO, Brazil.
José Clecildo B
JC
Bezerra
D003198:Computer Simulation; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000469:parasitology; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D010455:Peptides