Research Article
In Silico Search of Energy Metabolism Inhibitors for Alternative
Leishmaniasis Treatments
Lourival A. Silva,
1,2
Marina C. Vinaud,
2,3
Ana Maria Castro,
1,3
Pedro Vítor L. Cravo,
2,3
and José Clecildo B. Bezerra
2,3
1
Federal Institute of Education, Science and Technology of Goiˆ ania, 76300000 Ceres, GO, Brazil
2
Goi´ as Network of Research in Biotechnology and Metabolomics of the Host-Parasite Relationship,
Goi´ as Research Support Foundation (FAPEG), 74605050 Goiˆ ania, GO, Brazil
3
Institute of Tropical Pathology and Public Health, Federal University of Goi´ as, 74605050 Goiˆ ania, GO, Brazil
Correspondence should be addressed to Pedro V´ ıtor L. Cravo; pedrovcravo@gmail.com
Received 5 July 2014; Revised 8 August 2014; Accepted 14 September 2014
Academic Editor: Suresh Sundaram
Copyright © 2015 Lourival A. Silva et al. his is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Leishmaniasis is a complex disease that afects 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.
he current treatment for leishmaniasis is complex, expensive, and poorly eicacious. hus, there is an urgent need to develop
more selective, less expensive new drugs. he energy metabolism pathways of Leishmania include several interesting targets for
speciic 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, herapeutic Target Database (TTD), and PubChem
databases. We identiied 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.
1. Introduction
Leishmaniasis afects 12 million people worldwide, and
approximately 350 million people from 98 countries are at
risk of contracting the disease [1]. Leishmaniasis is caused by
approximately 20 distinct species of Leishmania and is trans-
mitted by two genera of phlebotomine sandlies: Phlebotomus
in the Old World and Lutzomyia in the New World. From a
clinical point of view, leishmaniasis is classiied as cutaneous,
mucocutaneous, or visceral; the latter is a severe form of the
disease that becomes fatal if let untreated [1, 2]. As efective
vaccines are unfortunately not available for either animals or
humans, prevention is restricted to the combat of vectors,
control of reservoirs, and treatment of afected individuals
[3, 4].
he drugs currently approved for the treatment of leish-
maniasis are directed at various molecular targets. Pentava-
lent antimonials interfere with the synthesis of DNA, -
oxidation of fatty acids, phosphorylation of ADP, and inhi-
bition of glycolysis. Amphotericin B exhibits a high ainity
for ergosterol, which is an important component of the cell
membrane in fungi and Leishmania. Miltefosine induces
apoptosis as a consequence of its intracellular accumulation.
Although paromomycin inhibits cytochrome C in Candida
krusei, its mechanism of action in Leishmania has not yet
been elucidated; it is believed that its site of action is in the
mitochondria, where it possibly interferes with the synthesis
of proteins by hindering the translocation and recycling
of ribosomal subunits. Pentamidine appears to reduce the
membrane potential and inhibits the enzyme topoisomerase
Hindawi Publishing Corporation
BioMed Research International
Volume 2015, Article ID 965725, 6 pages
http://dx.doi.org/10.1155/2015/965725