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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, ex...

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Autores principales: Silva, Lourival A., Vinaud, Marina C., Castro, Ana Maria, Cravo, Pedro Vítor L., Bezerra, José Clecildo B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396002/
https://www.ncbi.nlm.nih.gov/pubmed/25918726
http://dx.doi.org/10.1155/2015/965725
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author Silva, Lourival A.
Vinaud, Marina C.
Castro, Ana Maria
Cravo, Pedro Vítor L.
Bezerra, José Clecildo B.
author_facet Silva, Lourival A.
Vinaud, Marina C.
Castro, Ana Maria
Cravo, Pedro Vítor L.
Bezerra, José Clecildo B.
author_sort Silva, Lourival A.
collection PubMed
description 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.
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spelling pubmed-43960022015-04-27 In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments Silva, Lourival A. Vinaud, Marina C. Castro, Ana Maria Cravo, Pedro Vítor L. Bezerra, José Clecildo B. Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2015 2015-03-30 /pmc/articles/PMC4396002/ /pubmed/25918726 http://dx.doi.org/10.1155/2015/965725 Text en Copyright © 2015 Lourival A. Silva et al. https://creativecommons.org/licenses/by/3.0/ This 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.
spellingShingle Research Article
Silva, Lourival A.
Vinaud, Marina C.
Castro, Ana Maria
Cravo, Pedro Vítor L.
Bezerra, José Clecildo B.
In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments
title In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments
title_full In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments
title_fullStr In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments
title_full_unstemmed In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments
title_short In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments
title_sort in silico search of energy metabolism inhibitors for alternative leishmaniasis treatments
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396002/
https://www.ncbi.nlm.nih.gov/pubmed/25918726
http://dx.doi.org/10.1155/2015/965725
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