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Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae)
Protozoan parasites belonging to genera Leishmania and Trypanosoma are the etiological agents of severe neglected tropical diseases (NTDs) that cause enormous social and economic impact in many countries of tropical and sub-tropical areas of the world. In our screening program for new drug leads fro...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593781/ https://www.ncbi.nlm.nih.gov/pubmed/19079599 http://dx.doi.org/10.1371/journal.pntd.0000348 |
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author | Campos, Fernanda Fraga Rosa, Luiz Henrique Cota, Betania Barros Caligiorne, Rachel Basques Teles Rabello, Ana Lúcia Alves, Tânia Maria Almeida Rosa, Carlos Augusto Zani, Carlos Leomar |
author_facet | Campos, Fernanda Fraga Rosa, Luiz Henrique Cota, Betania Barros Caligiorne, Rachel Basques Teles Rabello, Ana Lúcia Alves, Tânia Maria Almeida Rosa, Carlos Augusto Zani, Carlos Leomar |
author_sort | Campos, Fernanda Fraga |
collection | PubMed |
description | Protozoan parasites belonging to genera Leishmania and Trypanosoma are the etiological agents of severe neglected tropical diseases (NTDs) that cause enormous social and economic impact in many countries of tropical and sub-tropical areas of the world. In our screening program for new drug leads from natural sources, we found that the crude extract of the endophytic fungus Cochliobolus sp. (UFMGCB-555) could kill 90% of the amastigote-like forms of Leishmania amazonensis and inhibit by 100% Ellman's reagent reduction in the trypanothione reductase (TryR) assay, when tested at 20 µg mL(−1). UFMGCB-555 was isolated from the plant Piptadenia adiantoides J.F. Macbr (Fabaceae) and identified based on the sequence of the internally transcribed spacer (ITS) regions of its ribosomal DNA. The chromatographic fractionation of the extract was guided by the TryR assay and resulted in the isolation of cochlioquinone A and isocochlioquinone A. Both compounds were active in the assay with L. amazonensis, disclosing EC(50) values (effective concentrations required to kill 50% of the parasite) of 1.7 µM (95% confidence interval = 1.6 to 1.9 µM) and 4.1 µM (95% confidence interval = 3.6 to 4.7 µM), respectively. These compounds were not active against three human cancer cell lines (MCF-7, TK-10, and UACC-62), indicating some degree of selectivity towards the parasites. These results suggest that cochlioquinones are attractive lead compounds that deserve further investigation aiming at developing new drugs to treat leishmaniasis. The findings also reinforce the role of endophytic fungi as an important source of compounds with potential to enter the pipeline for drug development against NTDs. |
format | Text |
id | pubmed-2593781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-25937812008-12-16 Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae) Campos, Fernanda Fraga Rosa, Luiz Henrique Cota, Betania Barros Caligiorne, Rachel Basques Teles Rabello, Ana Lúcia Alves, Tânia Maria Almeida Rosa, Carlos Augusto Zani, Carlos Leomar PLoS Negl Trop Dis Research Article Protozoan parasites belonging to genera Leishmania and Trypanosoma are the etiological agents of severe neglected tropical diseases (NTDs) that cause enormous social and economic impact in many countries of tropical and sub-tropical areas of the world. In our screening program for new drug leads from natural sources, we found that the crude extract of the endophytic fungus Cochliobolus sp. (UFMGCB-555) could kill 90% of the amastigote-like forms of Leishmania amazonensis and inhibit by 100% Ellman's reagent reduction in the trypanothione reductase (TryR) assay, when tested at 20 µg mL(−1). UFMGCB-555 was isolated from the plant Piptadenia adiantoides J.F. Macbr (Fabaceae) and identified based on the sequence of the internally transcribed spacer (ITS) regions of its ribosomal DNA. The chromatographic fractionation of the extract was guided by the TryR assay and resulted in the isolation of cochlioquinone A and isocochlioquinone A. Both compounds were active in the assay with L. amazonensis, disclosing EC(50) values (effective concentrations required to kill 50% of the parasite) of 1.7 µM (95% confidence interval = 1.6 to 1.9 µM) and 4.1 µM (95% confidence interval = 3.6 to 4.7 µM), respectively. These compounds were not active against three human cancer cell lines (MCF-7, TK-10, and UACC-62), indicating some degree of selectivity towards the parasites. These results suggest that cochlioquinones are attractive lead compounds that deserve further investigation aiming at developing new drugs to treat leishmaniasis. The findings also reinforce the role of endophytic fungi as an important source of compounds with potential to enter the pipeline for drug development against NTDs. Public Library of Science 2008-12-16 /pmc/articles/PMC2593781/ /pubmed/19079599 http://dx.doi.org/10.1371/journal.pntd.0000348 Text en Campos et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Campos, Fernanda Fraga Rosa, Luiz Henrique Cota, Betania Barros Caligiorne, Rachel Basques Teles Rabello, Ana Lúcia Alves, Tânia Maria Almeida Rosa, Carlos Augusto Zani, Carlos Leomar Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae) |
title | Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae) |
title_full | Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae) |
title_fullStr | Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae) |
title_full_unstemmed | Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae) |
title_short | Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae) |
title_sort | leishmanicidal metabolites from cochliobolus sp., an endophytic fungus isolated from piptadenia adiantoides (fabaceae) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593781/ https://www.ncbi.nlm.nih.gov/pubmed/19079599 http://dx.doi.org/10.1371/journal.pntd.0000348 |
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