Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos

Detalhes bibliográficos
Autor(a) principal: Meira, Cássio Santana
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UEFS
Texto Completo: http://localhost:8080/tede/handle/tede/110
Resumo: Chagas disease is a zoonosis caused by the hemoflagellate protozoan Trypanosoma cruzi, which affects millions of people in Latin America. Disease treatment is based on the use of two drugs, benznidazole and nifurtimox, which present low cure rates in the chronic phase of the disease as well as generating a number of adverse side effects. In this context, the development of new therapies for a better treatment of Chagas disease is necessary. In this study we investigated the anti-T.cruzi potential of physalins and betulinic acid, plant-based isolated steroids, in addition to synthetic derivatives from the latter, in in vitro assays. Our results demonstrate a high trypanocidal activity of physalins B and F and of the derivative BA5 against trypomastigote forms and on the processes of invasion and development of these on peritoneal macrophages. Electron microscopy revealed that physalin B or BA5 derivative treatment resulted in ultrastructural changes in the plasma membrane, Golgi apparatus, kinetoplast and endoplasmic reticulum of trypomastigotes forms. Additionally, these compounds contributed to the formation of atypical vacuoles in the appearance of myelin figures, which were labeled with MDC to confirm their identity as autophagic vacuoles. Flow cytometry analysis revealed that parasite death occurred mainly by necrosis. When combined with benznidazole, physalin B, physalin F or BA5 derivative, resulted in a higher anti-T. cruzi activity against amastigotes when compared to the compounds tested alone. These results indicate that steroids, such as physalins B and F and the derivative BA5, are potential candidates for an alternative treatment of Chagas disease.
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spelling Soares, Milena Botelho Pereira02911010540http://lattes.cnpq.br/5256812725884535Meira, Cássio Santana2015-07-28T00:17:52Z2014-02-05MEIRA, Cássio Santana. Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos. 2014. 157 f. Dissertação (Mestrado Acadêmico em Biotecnologia) - Universidade Estadual de Feira de Santana, Feira de Santana, 2014.http://localhost:8080/tede/handle/tede/110Chagas disease is a zoonosis caused by the hemoflagellate protozoan Trypanosoma cruzi, which affects millions of people in Latin America. Disease treatment is based on the use of two drugs, benznidazole and nifurtimox, which present low cure rates in the chronic phase of the disease as well as generating a number of adverse side effects. In this context, the development of new therapies for a better treatment of Chagas disease is necessary. In this study we investigated the anti-T.cruzi potential of physalins and betulinic acid, plant-based isolated steroids, in addition to synthetic derivatives from the latter, in in vitro assays. Our results demonstrate a high trypanocidal activity of physalins B and F and of the derivative BA5 against trypomastigote forms and on the processes of invasion and development of these on peritoneal macrophages. Electron microscopy revealed that physalin B or BA5 derivative treatment resulted in ultrastructural changes in the plasma membrane, Golgi apparatus, kinetoplast and endoplasmic reticulum of trypomastigotes forms. Additionally, these compounds contributed to the formation of atypical vacuoles in the appearance of myelin figures, which were labeled with MDC to confirm their identity as autophagic vacuoles. Flow cytometry analysis revealed that parasite death occurred mainly by necrosis. When combined with benznidazole, physalin B, physalin F or BA5 derivative, resulted in a higher anti-T. cruzi activity against amastigotes when compared to the compounds tested alone. These results indicate that steroids, such as physalins B and F and the derivative BA5, are potential candidates for an alternative treatment of Chagas disease.A doença de Chagas é uma zoonose causada pelo protozoário hemoflagelado Trypanosoma cruzi, que afeta milhões de pessoas na América Latina. O tratamento dessa enfermidade se baseia na utilização de dois fármacos, o benzonidazol e o nifurtimox, que possuem baixa taxa de cura na fase crônica da doença, além de gerarem uma série de efeitos colaterais. Nesse contexto, o surgimento de novos medicamentos para uma quimioterapia mais adequada da doença de Chagas torna-se necessário. Neste estudo investigamos o potencial anti-T. cruzi de esteroides isolados de plantas, fisalinas e ácido betulínico, assim como de derivados sintéticos deste último, em ensaios in vitro. Nossos resultados demonstram uma elevada atividade tripanocida das fisalinas B e F e do derivado BA5 contra formas tripomastigotas e sobre os processos de invasão e desenvolvimento destas em macrófagos peritoneais. Através de ensaios de microscopia eletrônica foi possível observar que o tratamento com a fisalina B ou com o derivado BA5 causa alterações ultraestruturais na membrana plasmática, complexo de Golgi, cinetoplasto e retículo endoplasmático das formas tripomastigotas, além da formação de vacúolos atípicos e o aparecimento de figuras mielínicas, que foram marcadas com MDC para confirmar a sua identidade como vacúolos autofágicos. Análises por citometria de fluxo revelaram que a morte parasitária ocorre principalmente por necrose. A combinação da fisalina B, da fisalina F ou do derivado BA5 com o benzonidazol resultou em uma maior atividade anti-T. cruzi frente a formas amastigotas quando comparados aos compostos testados de forma isolada. Estes resultados indicam que esteroides, tais como as fisalinas B e F e o derivado BA5, são potencias candidatos para o tratamento alternativo da doença de Chagas.Submitted by Natalie Mendes (nataliermendes@gmail.com) on 2015-07-28T00:17:52Z No. of bitstreams: 1 Dissertação - Cássio Santana.pdf: 10345998 bytes, checksum: 41cc3a308f7a72f1c4e10cc1ee2fe345 (MD5)Made available in DSpace on 2015-07-28T00:17:52Z (GMT). No. of bitstreams: 1 Dissertação - Cássio Santana.pdf: 10345998 bytes, checksum: 41cc3a308f7a72f1c4e10cc1ee2fe345 (MD5) Previous issue date: 2014-02-05Fundação de Amparo à Pesquisa do Estado da Bahia - FAPEBapplication/pdfporUniversidade Estadual de Feira de SantanaMestrado Acadêmico em BiotecnologiaUEFSBrasilDEPARTAMENTO DE CIÊNCIAS BIOLÓGICASDoença de ChagasTrypanosoma cruziEsteroidesFisalinasÁcido BetulínicoChagas DiseaseTrypanosoma cruziSteroidsPhysalinsBetulinic AcidCIENCIAS BIOLOGICASInvestigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis7701973706309601282600600600600-6971480722008537872-34391788430682021614767858349021390776info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UEFSinstname:Universidade Estadual de Feira de Santana (UEFS)instacron:UEFSORIGINALDissertação - Cássio Santana.pdfDissertação - Cássio Santana.pdfapplication/pdf10345998http://tede2.uefs.br:8080/bitstream/tede/110/2/Disserta%C3%A7%C3%A3o+-+C%C3%A1ssio+Santana.pdf41cc3a308f7a72f1c4e10cc1ee2fe345MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://tede2.uefs.br:8080/bitstream/tede/110/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51tede/1102016-01-13 20:52:29.727oai:tede2.uefs.br:8080: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.uefs.br:8080/PUBhttp://tede2.uefs.br:8080/oai/requestbcuefs@uefs.br|| bcref@uefs.br||bcuefs@uefs.bropendoar:2016-01-13T23:52:29Biblioteca Digital de Teses e Dissertações da UEFS - Universidade Estadual de Feira de Santana (UEFS)false
dc.title.por.fl_str_mv Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
title Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
spellingShingle Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
Meira, Cássio Santana
Doença de Chagas
Trypanosoma cruzi
Esteroides
Fisalinas
Ácido Betulínico
Chagas Disease
Trypanosoma cruzi
Steroids
Physalins
Betulinic Acid
CIENCIAS BIOLOGICAS
title_short Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
title_full Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
title_fullStr Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
title_full_unstemmed Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
title_sort Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos
author Meira, Cássio Santana
author_facet Meira, Cássio Santana
author_role author
dc.contributor.advisor1.fl_str_mv Soares, Milena Botelho Pereira
dc.contributor.authorID.fl_str_mv 02911010540
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5256812725884535
dc.contributor.author.fl_str_mv Meira, Cássio Santana
contributor_str_mv Soares, Milena Botelho Pereira
dc.subject.por.fl_str_mv Doença de Chagas
Trypanosoma cruzi
Esteroides
Fisalinas
Ácido Betulínico
topic Doença de Chagas
Trypanosoma cruzi
Esteroides
Fisalinas
Ácido Betulínico
Chagas Disease
Trypanosoma cruzi
Steroids
Physalins
Betulinic Acid
CIENCIAS BIOLOGICAS
dc.subject.eng.fl_str_mv Chagas Disease
Trypanosoma cruzi
Steroids
Physalins
Betulinic Acid
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS
description Chagas disease is a zoonosis caused by the hemoflagellate protozoan Trypanosoma cruzi, which affects millions of people in Latin America. Disease treatment is based on the use of two drugs, benznidazole and nifurtimox, which present low cure rates in the chronic phase of the disease as well as generating a number of adverse side effects. In this context, the development of new therapies for a better treatment of Chagas disease is necessary. In this study we investigated the anti-T.cruzi potential of physalins and betulinic acid, plant-based isolated steroids, in addition to synthetic derivatives from the latter, in in vitro assays. Our results demonstrate a high trypanocidal activity of physalins B and F and of the derivative BA5 against trypomastigote forms and on the processes of invasion and development of these on peritoneal macrophages. Electron microscopy revealed that physalin B or BA5 derivative treatment resulted in ultrastructural changes in the plasma membrane, Golgi apparatus, kinetoplast and endoplasmic reticulum of trypomastigotes forms. Additionally, these compounds contributed to the formation of atypical vacuoles in the appearance of myelin figures, which were labeled with MDC to confirm their identity as autophagic vacuoles. Flow cytometry analysis revealed that parasite death occurred mainly by necrosis. When combined with benznidazole, physalin B, physalin F or BA5 derivative, resulted in a higher anti-T. cruzi activity against amastigotes when compared to the compounds tested alone. These results indicate that steroids, such as physalins B and F and the derivative BA5, are potential candidates for an alternative treatment of Chagas disease.
publishDate 2014
dc.date.issued.fl_str_mv 2014-02-05
dc.date.accessioned.fl_str_mv 2015-07-28T00:17:52Z
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dc.identifier.citation.fl_str_mv MEIRA, Cássio Santana. Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos. 2014. 157 f. Dissertação (Mestrado Acadêmico em Biotecnologia) - Universidade Estadual de Feira de Santana, Feira de Santana, 2014.
dc.identifier.uri.fl_str_mv http://localhost:8080/tede/handle/tede/110
identifier_str_mv MEIRA, Cássio Santana. Investigação da atividade Anti-Trypanosoma Cruzi de esteroides isolados de plantas e derivados sintéticos. 2014. 157 f. Dissertação (Mestrado Acadêmico em Biotecnologia) - Universidade Estadual de Feira de Santana, Feira de Santana, 2014.
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