Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico

Detalhes bibliográficos
Autor(a) principal: Medeiros, César Augusto Costa de
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/123456789/23017
Resumo: Fungi comprise a group of pathogens that can cause serious health damage. Aspergillus flavus is among the main causes of serious comorbidities, among them, aspergillosis. Current afungal therapy has been increasingly inefficient, due to a series of issues related to adaptive mechanisms of the fungal cell itself or even due to toxicity associated with the high doses necessary for them to have the desired effect. In view of this, the search for new substances that may have antifungal effects through different mechanisms of action has been increasing. Natural products are a strong ally for these findings, since they are phytoconstituents of plant origin that have different biological activities. Among these, carvacrol stands out, a monoterpene found mainly in plants such as Origanum vulgare (oregano). Therefore, the objective of this work was to investigate the antifungal action of carvacrol and the licensed antifungals amphotericin B, fluconazole and voriconazole against clinical isolates of A. flavus. Assays to evaluate the biological activities were performed using the microdilution technique to determine the minimum inhibitory concentration (MIC), minimum fungicidal concentration (CFM), association studies and study of possible mechanisms of action. In the results of biological activity, it was observed that carvacrol at a concentration of 16 μg/ml inhibited the growth of most fungal strains, followed by amphotericin B, with MIC values of 32 μg/mL, fluconazole with 512 μg/mL and voriconazole with 1 μg/mL. As for the CFM assays, values of 32 μg/mL for carvacrol were observed, representing a fungicidal effect for the substance in question. Drug association assays are currently very well seen, because in addition to reducing the effective concentration of each substance, thus reducing the risk of toxicity, the use of more than one mechanism of action can be a very viable alternative in the fight against serious fungal pathologies. , thus, the association of carvacrol with amphotericin B represented ICIF values of 0.875, being considered an association of additivity. The proposed mechanism of action for carvacrol against A. flavus isolates was obtained from the sorbitol and ergosterol assays, where we can observe an action of the substance against the ergosterol of the fungal cell membrane, causing its imbalance and leading to cell death. fungal. Thus, carvacrol presents itself as a good candidate in the search for the development of new therapeutic alternatives that will meet the current needs in the face of the fungal pathologies in question.
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spelling Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológicoAspergillusInfecçõesFitoconstituinteCarvacrolInfectionsPhytoconstituentCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAFungi comprise a group of pathogens that can cause serious health damage. Aspergillus flavus is among the main causes of serious comorbidities, among them, aspergillosis. Current afungal therapy has been increasingly inefficient, due to a series of issues related to adaptive mechanisms of the fungal cell itself or even due to toxicity associated with the high doses necessary for them to have the desired effect. In view of this, the search for new substances that may have antifungal effects through different mechanisms of action has been increasing. Natural products are a strong ally for these findings, since they are phytoconstituents of plant origin that have different biological activities. Among these, carvacrol stands out, a monoterpene found mainly in plants such as Origanum vulgare (oregano). Therefore, the objective of this work was to investigate the antifungal action of carvacrol and the licensed antifungals amphotericin B, fluconazole and voriconazole against clinical isolates of A. flavus. Assays to evaluate the biological activities were performed using the microdilution technique to determine the minimum inhibitory concentration (MIC), minimum fungicidal concentration (CFM), association studies and study of possible mechanisms of action. In the results of biological activity, it was observed that carvacrol at a concentration of 16 μg/ml inhibited the growth of most fungal strains, followed by amphotericin B, with MIC values of 32 μg/mL, fluconazole with 512 μg/mL and voriconazole with 1 μg/mL. As for the CFM assays, values of 32 μg/mL for carvacrol were observed, representing a fungicidal effect for the substance in question. Drug association assays are currently very well seen, because in addition to reducing the effective concentration of each substance, thus reducing the risk of toxicity, the use of more than one mechanism of action can be a very viable alternative in the fight against serious fungal pathologies. , thus, the association of carvacrol with amphotericin B represented ICIF values of 0.875, being considered an association of additivity. The proposed mechanism of action for carvacrol against A. flavus isolates was obtained from the sorbitol and ergosterol assays, where we can observe an action of the substance against the ergosterol of the fungal cell membrane, causing its imbalance and leading to cell death. fungal. Thus, carvacrol presents itself as a good candidate in the search for the development of new therapeutic alternatives that will meet the current needs in the face of the fungal pathologies in question.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqOs fungos compreendem um grupo de patógenos que podem causar sérios danos à saúde. Aspergillus flavus está entre os principais agentes de comorbidades sérias, dentre elas, as aspergiloses. A terapia antifúngica atual tem se apresentando cada vez mais ineficiente, devido uma série de questões relacionadas a mecanismos adaptativos da própria célula fúngica, bem como da toxicidade associada às altas doses necessárias para o efeito desejado. Diante disto, a pesquisa por novas substâncias com atividade antifúngica por diferentes mecanismos de ação vem se tornando cada vez crescente. Os produtos naturais apresentam-se como um forte aliado para estes achados, visto que são fitoconstituintes que apresentam diversas atividades biológicas. Dentre estes, destaca-se o carvacrol, um monoterpeno encontrado principalmente em plantas como Origanum vulgare (orégano). Sendo assim, o objetivo deste trabalho foi investigar a ação antifúngica do carvacrol comparado a antifúngicos padrões anfotericina B, fluconazol e voriconazol frente a isolados clínicos de A. flavus. Os ensaios para avaliar as atividades biológicas foram realizadas pela técnica de microdiluição para determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), estudos de associação e estudo dos possíveis mecanismos de ação. Nos resultados de atividade biológica foi observado que o carvacrol na concentração de 16 μg/ml inibiu o crescimento da maioria das cepas fúngicas, seguido da anfotericina B, com valores de CIM de 32 μg/mL fluconazol com 512 μg/mL e voriconazol com 1 μg/mL. Quanto aos ensaios de CFM, valores de 32 μg/mL para o carvacrol foram observados, representando efeito fungicida para a substância em questão. A associação de carvacrol com anfotericina B representou valores de ICIF de 0,875, considerada de aditividade. O mecanismo de ação proposto para o carvacrol frente aos isolados de A. flavus foi obtido a partir dos ensaios de sorbitol e ergosterol, onde foi observada ação frente ao ergosterol da membrana celular fúngica. Dessa forma, carvacrol apresenta-se como bom candidato na busca do desenvolvimento de novas alternativas terapêuticas que venham a suprir as necessidades atuais frente as patologias fúngicas em questão.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBLima, Edeltrudes de Oliveirahttp://lattes.cnpq.br/9406572870167006Medeiros, César Augusto Costa de2022-06-06T20:21:33Z2022-03-212022-06-06T20:21:33Z2022-02-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/23017porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2022-08-09T14:15:31Zoai:repositorio.ufpb.br:123456789/23017Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2022-08-09T14:15:31Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
title Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
spellingShingle Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
Medeiros, César Augusto Costa de
Aspergillus
Infecções
Fitoconstituinte
Carvacrol
Infections
Phytoconstituent
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
title_full Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
title_fullStr Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
title_full_unstemmed Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
title_sort Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico
author Medeiros, César Augusto Costa de
author_facet Medeiros, César Augusto Costa de
author_role author
dc.contributor.none.fl_str_mv Lima, Edeltrudes de Oliveira
http://lattes.cnpq.br/9406572870167006
dc.contributor.author.fl_str_mv Medeiros, César Augusto Costa de
dc.subject.por.fl_str_mv Aspergillus
Infecções
Fitoconstituinte
Carvacrol
Infections
Phytoconstituent
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Aspergillus
Infecções
Fitoconstituinte
Carvacrol
Infections
Phytoconstituent
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Fungi comprise a group of pathogens that can cause serious health damage. Aspergillus flavus is among the main causes of serious comorbidities, among them, aspergillosis. Current afungal therapy has been increasingly inefficient, due to a series of issues related to adaptive mechanisms of the fungal cell itself or even due to toxicity associated with the high doses necessary for them to have the desired effect. In view of this, the search for new substances that may have antifungal effects through different mechanisms of action has been increasing. Natural products are a strong ally for these findings, since they are phytoconstituents of plant origin that have different biological activities. Among these, carvacrol stands out, a monoterpene found mainly in plants such as Origanum vulgare (oregano). Therefore, the objective of this work was to investigate the antifungal action of carvacrol and the licensed antifungals amphotericin B, fluconazole and voriconazole against clinical isolates of A. flavus. Assays to evaluate the biological activities were performed using the microdilution technique to determine the minimum inhibitory concentration (MIC), minimum fungicidal concentration (CFM), association studies and study of possible mechanisms of action. In the results of biological activity, it was observed that carvacrol at a concentration of 16 μg/ml inhibited the growth of most fungal strains, followed by amphotericin B, with MIC values of 32 μg/mL, fluconazole with 512 μg/mL and voriconazole with 1 μg/mL. As for the CFM assays, values of 32 μg/mL for carvacrol were observed, representing a fungicidal effect for the substance in question. Drug association assays are currently very well seen, because in addition to reducing the effective concentration of each substance, thus reducing the risk of toxicity, the use of more than one mechanism of action can be a very viable alternative in the fight against serious fungal pathologies. , thus, the association of carvacrol with amphotericin B represented ICIF values of 0.875, being considered an association of additivity. The proposed mechanism of action for carvacrol against A. flavus isolates was obtained from the sorbitol and ergosterol assays, where we can observe an action of the substance against the ergosterol of the fungal cell membrane, causing its imbalance and leading to cell death. fungal. Thus, carvacrol presents itself as a good candidate in the search for the development of new therapeutic alternatives that will meet the current needs in the face of the fungal pathologies in question.
publishDate 2022
dc.date.none.fl_str_mv 2022-06-06T20:21:33Z
2022-03-21
2022-06-06T20:21:33Z
2022-02-21
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/23017
url https://repositorio.ufpb.br/jspui/handle/123456789/23017
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
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instname_str Universidade Federal da Paraíba (UFPB)
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repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
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