Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L.
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | LOCUS Repositório Institucional da UFV |
Texto Completo: | https://doi.org/10.1016/j.ejmech.2016.08.030 http://www.locus.ufv.br/handle/123456789/19428 |
Resumo: | Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries that affect more than 12 million people. Current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, the search for new effective and less toxic treatments is an urgent need. In this study, we report the synthesis of 3 new amide derivatives of hederagenin (22–24) with yields between 70% and 90%, along with 57 other derivatives of hederagenin (1–21, 25–60) carrying different groups at C-28 previously reported by our group, and the results of their in vitro ability to inhibit the growth of Leishmania infantum. Some derivatives (3, 4, 44, 49 and 52), showed activity at micromolar level and low toxicity against BGM and HepG2 cells. Moreover, the ability of hederagenin derivatives 3 (IC50 = 9.7 μM), 4 (12 μM), 44 (11 μM) and 49 (2 μM), to prevent proliferation of intracellular amastigote forms of L. infantum and their higher selectivity index and low toxicity compared to commercial positive drug control of choice (potassium antimonyl tartrate trihydrate) (IC50 = 80 μM, SI = 0.1), make these compounds promising candidates for the treatment of leishmaniasis. |
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Rodríguez-Hernández, DiegoBarbosa, Luiz C.A.Demuner, Antonio J.Almeida, Raquel M.deFujiwara, Ricardo T.Ferreira, Sebastião R.2018-05-09T18:23:06Z2018-05-09T18:23:06Z2016-11-2902235234https://doi.org/10.1016/j.ejmech.2016.08.030http://www.locus.ufv.br/handle/123456789/19428Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries that affect more than 12 million people. Current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, the search for new effective and less toxic treatments is an urgent need. In this study, we report the synthesis of 3 new amide derivatives of hederagenin (22–24) with yields between 70% and 90%, along with 57 other derivatives of hederagenin (1–21, 25–60) carrying different groups at C-28 previously reported by our group, and the results of their in vitro ability to inhibit the growth of Leishmania infantum. Some derivatives (3, 4, 44, 49 and 52), showed activity at micromolar level and low toxicity against BGM and HepG2 cells. Moreover, the ability of hederagenin derivatives 3 (IC50 = 9.7 μM), 4 (12 μM), 44 (11 μM) and 49 (2 μM), to prevent proliferation of intracellular amastigote forms of L. infantum and their higher selectivity index and low toxicity compared to commercial positive drug control of choice (potassium antimonyl tartrate trihydrate) (IC50 = 80 μM, SI = 0.1), make these compounds promising candidates for the treatment of leishmaniasis.engEuropean Journal of Medicinal Chemistryv. 124, p. 153-159, 2016Elsevier Masson SAS.info:eu-repo/semantics/openAccessPentacyclic triterpenesHederagenin derivativesLeihmania infantumAnti-leishmanial activityTriazole compoundsHighly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfreponame:LOCUS Repositório Institucional da UFVinstname:Universidade Federal de Viçosa (UFV)instacron:UFVORIGINALartigo.pdfartigo.pdftexto completoapplication/pdf723331https://locus.ufv.br//bitstream/123456789/19428/1/artigo.pdf5be15cb75d2711a399c09dda080081fbMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://locus.ufv.br//bitstream/123456789/19428/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILartigo.pdf.jpgartigo.pdf.jpgIM Thumbnailimage/jpeg6436https://locus.ufv.br//bitstream/123456789/19428/3/artigo.pdf.jpg4c93d15345389020b837de84057976ecMD53123456789/194282018-05-09 23:00:44.282oai:locus.ufv.br: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Repositório InstitucionalPUBhttps://www.locus.ufv.br/oai/requestfabiojreis@ufv.bropendoar:21452018-05-10T02:00:44LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV)false |
dc.title.en.fl_str_mv |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. |
title |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. |
spellingShingle |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. Rodríguez-Hernández, Diego Pentacyclic triterpenes Hederagenin derivatives Leihmania infantum Anti-leishmanial activity Triazole compounds |
title_short |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. |
title_full |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. |
title_fullStr |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. |
title_full_unstemmed |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. |
title_sort |
Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L. |
author |
Rodríguez-Hernández, Diego |
author_facet |
Rodríguez-Hernández, Diego Barbosa, Luiz C.A. Demuner, Antonio J. Almeida, Raquel M.de Fujiwara, Ricardo T. Ferreira, Sebastião R. |
author_role |
author |
author2 |
Barbosa, Luiz C.A. Demuner, Antonio J. Almeida, Raquel M.de Fujiwara, Ricardo T. Ferreira, Sebastião R. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Rodríguez-Hernández, Diego Barbosa, Luiz C.A. Demuner, Antonio J. Almeida, Raquel M.de Fujiwara, Ricardo T. Ferreira, Sebastião R. |
dc.subject.pt-BR.fl_str_mv |
Pentacyclic triterpenes Hederagenin derivatives Leihmania infantum Anti-leishmanial activity Triazole compounds |
topic |
Pentacyclic triterpenes Hederagenin derivatives Leihmania infantum Anti-leishmanial activity Triazole compounds |
description |
Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries that affect more than 12 million people. Current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, the search for new effective and less toxic treatments is an urgent need. In this study, we report the synthesis of 3 new amide derivatives of hederagenin (22–24) with yields between 70% and 90%, along with 57 other derivatives of hederagenin (1–21, 25–60) carrying different groups at C-28 previously reported by our group, and the results of their in vitro ability to inhibit the growth of Leishmania infantum. Some derivatives (3, 4, 44, 49 and 52), showed activity at micromolar level and low toxicity against BGM and HepG2 cells. Moreover, the ability of hederagenin derivatives 3 (IC50 = 9.7 μM), 4 (12 μM), 44 (11 μM) and 49 (2 μM), to prevent proliferation of intracellular amastigote forms of L. infantum and their higher selectivity index and low toxicity compared to commercial positive drug control of choice (potassium antimonyl tartrate trihydrate) (IC50 = 80 μM, SI = 0.1), make these compounds promising candidates for the treatment of leishmaniasis. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-11-29 |
dc.date.accessioned.fl_str_mv |
2018-05-09T18:23:06Z |
dc.date.available.fl_str_mv |
2018-05-09T18:23:06Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.1016/j.ejmech.2016.08.030 http://www.locus.ufv.br/handle/123456789/19428 |
dc.identifier.issn.none.fl_str_mv |
02235234 |
identifier_str_mv |
02235234 |
url |
https://doi.org/10.1016/j.ejmech.2016.08.030 http://www.locus.ufv.br/handle/123456789/19428 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofseries.pt-BR.fl_str_mv |
v. 124, p. 153-159, 2016 |
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Elsevier Masson SAS. info:eu-repo/semantics/openAccess |
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Elsevier Masson SAS. |
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openAccess |
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European Journal of Medicinal Chemistry |
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European Journal of Medicinal Chemistry |
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