Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans

Detalhes bibliográficos
Autor(a) principal: Freitas, Vivianny Aparecida Queiroz
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
dARK ID: ark:/38995/001300000065n
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/7402
Resumo: Cryptococcosis is a fungal disease caused by yeasts belonging to the complex Cryptococus neoformans. The antifungal arsenal available for the treatment of this disease is still restricted and is related to the high toxicity and side effects of some drugs, causing great harm to the patients. In this context, it is necessary to discover new bioactives to quell the infections and reduce the adverse effects. The plants have rich source of secondary bioactive metabolites such as tannins, terpenoids, saponins, alkaloids, flavonoids and other compounds, registered with expressive antimicrobial properties. Therefore, the research of natural compounds and derivatives of natural products has been relevant in recent years, due to their relevance in the discovery of new drugs, in addition to which the association of drugs or compounds with different mechanisms of action has been used as an alternative in conventional therapy. We evaluated the mechanisms of action and antifungal effect of natural compounds, curcumin and morin, on Cryptococcus neoformans and Cryptococcus gattii isolates. The antifungal activity was determined across the minimum inhibitory concentration (MIC) and minimum fungicide (MFC). Polyphenols showed MICs ranging from 2 to 256 μg/mL. The compounds showed a synergistic interaction in 30% (6/20) and 15% (3/20) of the isolates when dealing with morin and curcumin, respectively, associated with fluconazole. In the interaction with amphotericin B morin presented synergism in 70% (14/20) of the isolates. Both compounds did not exhibit antagonism in any of the combinations. Changes in fungal cell morphology were observed, and in contact with red blood cells, presented low toxicity. The mechanisms of action revealed that both polyphenols act on the membrane of the fungal cell, inhibiting the synthesis of ergosterol and causing damage to it. These results demonstrate the potential of the compounds as natural bioactives, with great impact on the discovery of new drugs and their efficacy to be used in the treatment of fungal infections.
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spelling Fernandes, Orionalda de Fátima Lisboahttp://lattes.cnpq.br/9826992750728262Fernandes, Orionalda de Fátima LisboaSouza, Lucia Kioko Hasimoto eMelhem, Márcia de Souza Carvalhohttp://lattes.cnpq.br/7773724647022741Freitas, Vivianny Aparecida Queiroz2017-06-02T11:13:05Z2017-05-12FREITAS, V. A. Q. Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans. 2017. 116 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) Universidade Federal de Goiás, Goiânia, 2017.http://repositorio.bc.ufg.br/tede/handle/tede/7402ark:/38995/001300000065nCryptococcosis is a fungal disease caused by yeasts belonging to the complex Cryptococus neoformans. The antifungal arsenal available for the treatment of this disease is still restricted and is related to the high toxicity and side effects of some drugs, causing great harm to the patients. In this context, it is necessary to discover new bioactives to quell the infections and reduce the adverse effects. The plants have rich source of secondary bioactive metabolites such as tannins, terpenoids, saponins, alkaloids, flavonoids and other compounds, registered with expressive antimicrobial properties. Therefore, the research of natural compounds and derivatives of natural products has been relevant in recent years, due to their relevance in the discovery of new drugs, in addition to which the association of drugs or compounds with different mechanisms of action has been used as an alternative in conventional therapy. We evaluated the mechanisms of action and antifungal effect of natural compounds, curcumin and morin, on Cryptococcus neoformans and Cryptococcus gattii isolates. The antifungal activity was determined across the minimum inhibitory concentration (MIC) and minimum fungicide (MFC). Polyphenols showed MICs ranging from 2 to 256 μg/mL. The compounds showed a synergistic interaction in 30% (6/20) and 15% (3/20) of the isolates when dealing with morin and curcumin, respectively, associated with fluconazole. In the interaction with amphotericin B morin presented synergism in 70% (14/20) of the isolates. Both compounds did not exhibit antagonism in any of the combinations. Changes in fungal cell morphology were observed, and in contact with red blood cells, presented low toxicity. The mechanisms of action revealed that both polyphenols act on the membrane of the fungal cell, inhibiting the synthesis of ergosterol and causing damage to it. These results demonstrate the potential of the compounds as natural bioactives, with great impact on the discovery of new drugs and their efficacy to be used in the treatment of fungal infections.A Criptococose é uma doença fúngica causada por leveduras pertencentes ao complexo Cryptococus neoformans. O arsenal antifúngico disponível para o tratamento dessa doença ainda é restrito e está relacionado à elevada toxicidade e efeitos colaterais de alguns fármacos, causando grande prejuízo aos pacientes Neste contexto, se faz necessário descobrir novos bioativos para debelar as infecções e reduzir os efeitos adversos. As plantas apresentam rica fonte de metabólitos secundários bioativos como taninos, terpenóides, saponinas, alcalóides, flavonoides e outros compostos, registrados com expressiva propriedade antimicrobiana. Portanto, a pesquisa de compostos naturais e derivados de produtos naturais tem sido pertinente nos últimos anos, devido à sua relevância na descoberta de novos medicamentos, além do que, a associação de fármacos ou compostos, com diferentes mecanismos de ação tem sido utilizada como alternativa na terapia convencional. Nós avaliamos os mecanismos de ação e o efeito antifúngico dos compostos naturais, curcumina e morina, sobre isolados de Cryptococcus neoformans e Cryptococcus gattii. A atividade antifúngica foi averiguada através da determinação da concentração inibitória mínima (CIM) e fungicida mínima (CFM). Os polifenóis, apresentaram CIMs que variaram de 2 a 256 μg/mL. Os compostos apresentaram interação sinérgica em 30% (6/20) e 15%(3/20) dos isolados se tratando da morina e curcumina, respectivamente, associada ao fluconazol. Na interação com a anfotericina B a morina apresentou sinergismo em 70% (14/20) dos isolados. Ambos os compostos não apresentaram antagonismo em nenhuma das combinações. Alterações na morfologia da célula fúngica foram observadas, e em contato com as hemácias, apresentaram baixa toxicidade. Os ensaios de mecanismos de ação revelaram que ambos os polifenóis atuam na membrana da célula fúngica inibindo a síntese de ergosterol e causando danos a mesma. Estes resultados demonstram o potencial dos compostos como bioativos naturais, apresentando grande impacto na descoberta de novos fármacos e sua eficácia para serem utilizados no tratamento de infecções fúngicas.Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-06-01T22:28:55Z No. of bitstreams: 2 Dissertação - Vivianny Aparecida Queiroz Freitas - 2017.pdf: 4680258 bytes, checksum: 0e08c83bdb454e044ddcef0daedb874a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-06-02T11:13:05Z (GMT) No. of bitstreams: 2 Dissertação - Vivianny Aparecida Queiroz Freitas - 2017.pdf: 4680258 bytes, checksum: 0e08c83bdb454e044ddcef0daedb874a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2017-06-02T11:13:05Z (GMT). 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dc.title.eng.fl_str_mv Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
dc.title.alternative.eng.fl_str_mv Action of curcumin and morin in yeasts of the Cryptococcus neoformans Complex
title Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
spellingShingle Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
Freitas, Vivianny Aparecida Queiroz
Curcumina
Morina
Cryptococcus neoformans
Curcumin
Morin
CIENCIAS BIOLOGICAS::MICROBIOLOGIA
title_short Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
title_full Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
title_fullStr Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
title_full_unstemmed Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
title_sort Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
author Freitas, Vivianny Aparecida Queiroz
author_facet Freitas, Vivianny Aparecida Queiroz
author_role author
dc.contributor.advisor1.fl_str_mv Fernandes, Orionalda de Fátima Lisboa
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9826992750728262
dc.contributor.referee1.fl_str_mv Fernandes, Orionalda de Fátima Lisboa
dc.contributor.referee2.fl_str_mv Souza, Lucia Kioko Hasimoto e
dc.contributor.referee3.fl_str_mv Melhem, Márcia de Souza Carvalho
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7773724647022741
dc.contributor.author.fl_str_mv Freitas, Vivianny Aparecida Queiroz
contributor_str_mv Fernandes, Orionalda de Fátima Lisboa
Fernandes, Orionalda de Fátima Lisboa
Souza, Lucia Kioko Hasimoto e
Melhem, Márcia de Souza Carvalho
dc.subject.por.fl_str_mv Curcumina
Morina
Cryptococcus neoformans
topic Curcumina
Morina
Cryptococcus neoformans
Curcumin
Morin
CIENCIAS BIOLOGICAS::MICROBIOLOGIA
dc.subject.eng.fl_str_mv Curcumin
Morin
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::MICROBIOLOGIA
description Cryptococcosis is a fungal disease caused by yeasts belonging to the complex Cryptococus neoformans. The antifungal arsenal available for the treatment of this disease is still restricted and is related to the high toxicity and side effects of some drugs, causing great harm to the patients. In this context, it is necessary to discover new bioactives to quell the infections and reduce the adverse effects. The plants have rich source of secondary bioactive metabolites such as tannins, terpenoids, saponins, alkaloids, flavonoids and other compounds, registered with expressive antimicrobial properties. Therefore, the research of natural compounds and derivatives of natural products has been relevant in recent years, due to their relevance in the discovery of new drugs, in addition to which the association of drugs or compounds with different mechanisms of action has been used as an alternative in conventional therapy. We evaluated the mechanisms of action and antifungal effect of natural compounds, curcumin and morin, on Cryptococcus neoformans and Cryptococcus gattii isolates. The antifungal activity was determined across the minimum inhibitory concentration (MIC) and minimum fungicide (MFC). Polyphenols showed MICs ranging from 2 to 256 μg/mL. The compounds showed a synergistic interaction in 30% (6/20) and 15% (3/20) of the isolates when dealing with morin and curcumin, respectively, associated with fluconazole. In the interaction with amphotericin B morin presented synergism in 70% (14/20) of the isolates. Both compounds did not exhibit antagonism in any of the combinations. Changes in fungal cell morphology were observed, and in contact with red blood cells, presented low toxicity. The mechanisms of action revealed that both polyphenols act on the membrane of the fungal cell, inhibiting the synthesis of ergosterol and causing damage to it. These results demonstrate the potential of the compounds as natural bioactives, with great impact on the discovery of new drugs and their efficacy to be used in the treatment of fungal infections.
publishDate 2017
dc.date.accessioned.fl_str_mv 2017-06-02T11:13:05Z
dc.date.issued.fl_str_mv 2017-05-12
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dc.identifier.citation.fl_str_mv FREITAS, V. A. Q. Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans. 2017. 116 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) Universidade Federal de Goiás, Goiânia, 2017.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/7402
dc.identifier.dark.fl_str_mv ark:/38995/001300000065n
identifier_str_mv FREITAS, V. A. Q. Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans. 2017. 116 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) Universidade Federal de Goiás, Goiânia, 2017.
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