Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi

Detalhes bibliográficos
Autor(a) principal: Souza Neta, Lourdes Cardoso de
Data de Publicação: 2014
Outros Autores: Menezes, Diego Silva, Lima, Milena da Silva, Cerqueira, Martins Dias de, Cruz, Frederico Guaré, Martins, Dirceu, Santos, Marcos André Vannier dos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/8472
Resumo: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Química. Grupo de Estudo de Produtos Naturais. Salvador, BA, Brasil
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spelling Souza Neta, Lourdes Cardoso deMenezes, Diego SilvaLima, Milena da SilvaCerqueira, Martins Dias deCruz, Frederico GuaréMartins, DirceuSantos, Marcos André Vannier dos2014-09-29T19:10:56Z2014-09-29T19:10:56Z2014SOUZA-NETA, L. C. et al. Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi. Current Topics in Medicinal Chemistry, v. 14, p. 1022-1032, 2014.1568-0266https://www.arca.fiocruz.br/handle/icict/8472engBentham Science PublishersModes of action of arjunolic acid and derivatives on Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Química. Grupo de Estudo de Produtos Naturais. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Química. Grupo de Estudo de Produtos Naturais. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Química. Grupo de Estudo de Produtos Naturais. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Química. Grupo de Estudo de Produtos Naturais. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Química. Grupo de Estudo de Produtos Naturais. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Conselho Nacional de Desenvolvimento Científico e Tecnológico/ Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica. Amazonia, MA, BrasilChagas disease causes considerable morbimortality in the Americas, with circa 7 to 8 million infected people, causing at least 12,000 annual deaths and 100 million people at risk. Its chemotherapy is poorly selective and effective, associated to severe side effects and unresponsive cases. Thus, R&D on therapeutic alternatives is undoubtedly required. The Brazilian poorly studied biodiversity offers uncountable bioagents, which may be exploited for chemotherapy. The triterpene arjunolic acid (AA), reduced the Trypanosoma cruzi epimastigote in vitro proliferation with an apparent IC50 of 171 μM. Electron microscopy analysis revealed remarkable effects on the parasite surface and architecture. AA-treated parasites displayed minutely corrugated plasma membranes devoid of subpellicular microtubules as well as biogenesis of multiple basal bodies. As the AA effects appeared mainly restricted or originated at the parasite peripheral cytoplasm, including the cytoskeleton membrane linkage, we inferred that the compound targeted primarily the lipid bilayer; therefore, we performed synthetic modification to increase the molecule lipophilicity and thus membrane permeability. The methyl ester (MeAA) and tri-acetylated derivatives (3AcAA) had potentiated trypanocidal activity, producing IC50 values of 21.9 and 15.8 μM, respectively. Both derivatives were able to produce remarkable ultrastructural alterations in the parasites, including inner compartments such as Golgi apparatus and the endocytic/autophagic pathway. Parasites cultured with both derivatives displayed numerous and large autophagic vacuoles, altered flagellar length and cell body connection. These data indicate that synthetically-modified natural products comprise valuable tools in antiparasitic chemotherapy and that electron microscopy may be useful not only in determining the mechanisms of action but also in directing such modifications for rational drug design.ChemotherapyElectron microscopyNatural productsTriterpeneTrypanosoma cruziinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8472/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALSouza-Neta LC Modes of action of arjunolic......pdfSouza-Neta LC Modes of action of arjunolic......pdfapplication/pdf1089939https://www.arca.fiocruz.br/bitstream/icict/8472/2/Souza-Neta%20LC%20Modes%20of%20action%20of%20arjunolic......pdf0dc91f8969576cc5716b0de98c6fbc6dMD52TEXTSouza-Neta LC Modes of action of arjunolic......pdf.txtSouza-Neta LC Modes of action of arjunolic......pdf.txtExtracted texttext/plain59549https://www.arca.fiocruz.br/bitstream/icict/8472/3/Souza-Neta%20LC%20Modes%20of%20action%20of%20arjunolic......pdf.txt749f8301c3d1b05b8c7dd931df5cdcb8MD53icict/84722023-03-15 14:33:23.98oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:23Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
title Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
spellingShingle Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
Souza Neta, Lourdes Cardoso de
Chemotherapy
Electron microscopy
Natural products
Triterpene
Trypanosoma cruzi
title_short Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
title_full Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
title_fullStr Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
title_full_unstemmed Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
title_sort Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi
author Souza Neta, Lourdes Cardoso de
author_facet Souza Neta, Lourdes Cardoso de
Menezes, Diego Silva
Lima, Milena da Silva
Cerqueira, Martins Dias de
Cruz, Frederico Guaré
Martins, Dirceu
Santos, Marcos André Vannier dos
author_role author
author2 Menezes, Diego Silva
Lima, Milena da Silva
Cerqueira, Martins Dias de
Cruz, Frederico Guaré
Martins, Dirceu
Santos, Marcos André Vannier dos
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Souza Neta, Lourdes Cardoso de
Menezes, Diego Silva
Lima, Milena da Silva
Cerqueira, Martins Dias de
Cruz, Frederico Guaré
Martins, Dirceu
Santos, Marcos André Vannier dos
dc.subject.en.pt_BR.fl_str_mv Chemotherapy
Electron microscopy
Natural products
Triterpene
Trypanosoma cruzi
topic Chemotherapy
Electron microscopy
Natural products
Triterpene
Trypanosoma cruzi
description Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Química. Grupo de Estudo de Produtos Naturais. Salvador, BA, Brasil
publishDate 2014
dc.date.accessioned.fl_str_mv 2014-09-29T19:10:56Z
dc.date.available.fl_str_mv 2014-09-29T19:10:56Z
dc.date.issued.fl_str_mv 2014
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.citation.fl_str_mv SOUZA-NETA, L. C. et al. Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi. Current Topics in Medicinal Chemistry, v. 14, p. 1022-1032, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/8472
dc.identifier.issn.none.fl_str_mv 1568-0266
identifier_str_mv SOUZA-NETA, L. C. et al. Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi. Current Topics in Medicinal Chemistry, v. 14, p. 1022-1032, 2014.
1568-0266
url https://www.arca.fiocruz.br/handle/icict/8472
dc.language.iso.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
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instname:Fundação Oswaldo Cruz (FIOCRUZ)
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collection Repositório Institucional da FIOCRUZ (ARCA)
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