Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/26118 |
Resumo: | Infections caused by the Candida genus, especially systemic ones, represent a challenge for public health due to high morbidity and mortality, high associated costs and difficulty in treatment with a good clinical prognosis. Candida albicans is the most frequent cause of this infection, however, the number of cases caused by non-albicans species such as C. parapsilosis has emerged, with a remarkable record of resistant strains. The search for new therapeutic alternatives becomes an important resource in the control of these infections and the use of some already known substances, such as 2-chloro-N-phenylacetamide, is a way to obtain potentially effective new products. Therefore, the antifungal potential of 2-chloro-N-phenylacetamide was investigated against fluconazole-resistant C. albicans and C. parapsilosis strains. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory and fungicidal concentrations (MIC and MFC), inhibition of biofilm formation and its rupture, investigation of the possible mechanism of action, and association between this molecule and amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 μg.mL-1, and a MFC of 512 to 1,024 μg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. However, 2-chloro-N-phenylacetamide did not promote antifungal activity by binding to cell membrane ergosterol, nor did it impair the integrity of the fungal cell wall. Antagonism has been observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal effects by inhibiting both planktonic cells and the biofilm of fluconazole-resistant strains. It is worth noting that its combination with other antifungals should be avoided and that its mechanism of action remains to be established. |
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Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazolFungicidas2-cloro-N-fenilacetamidaBiofilmeCandida spp.Resistência antifúngicaFungicides2-chloro-N-phenylacetamideBiofilmAntifungal resistanceMecanismo de açãoMechanism of actionCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAInfections caused by the Candida genus, especially systemic ones, represent a challenge for public health due to high morbidity and mortality, high associated costs and difficulty in treatment with a good clinical prognosis. Candida albicans is the most frequent cause of this infection, however, the number of cases caused by non-albicans species such as C. parapsilosis has emerged, with a remarkable record of resistant strains. The search for new therapeutic alternatives becomes an important resource in the control of these infections and the use of some already known substances, such as 2-chloro-N-phenylacetamide, is a way to obtain potentially effective new products. Therefore, the antifungal potential of 2-chloro-N-phenylacetamide was investigated against fluconazole-resistant C. albicans and C. parapsilosis strains. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory and fungicidal concentrations (MIC and MFC), inhibition of biofilm formation and its rupture, investigation of the possible mechanism of action, and association between this molecule and amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 μg.mL-1, and a MFC of 512 to 1,024 μg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. However, 2-chloro-N-phenylacetamide did not promote antifungal activity by binding to cell membrane ergosterol, nor did it impair the integrity of the fungal cell wall. Antagonism has been observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal effects by inhibiting both planktonic cells and the biofilm of fluconazole-resistant strains. It is worth noting that its combination with other antifungals should be avoided and that its mechanism of action remains to be established.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESInfecções causadas pelo gênero Candida, sobretudo as sistêmicas, representam um desafio para a saúde pública devido à alta morbimortalidade, elevados custos associados e dificuldade de tratamento com bom prognóstico clínico. Candida albicans é a mais frequente causadora desta infecção, entretanto, o número de casos provocados por espécies não-albicans como C. parapsilosis tem surgido, com notável registro de linhagens resistentes. A busca por novas alternativas terapêuticas se torna um recurso importante no controle destas infecções e o aproveitamento de algumas substâncias já conhecidas, como a 2-cloro-N-fenilacetamida, é uma maneira de se obter novos produtos potencialmente eficazes. Diante disto, o potencial antifúngico da 2-cloro-N-fenilacetamida foi investigado contra linhagens de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da 2-cloro-N-fenilacetamida foi avaliada in vitro pela determinação da concentração inibitória e fungicida mínima (CIM e CFM), inibição da formação de biofilme e sua ruptura, investigação de provável mecanismo de ação e associação desta molécula com anfotericina B e fluconazol. O produto teste inibiu o crescimento de todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 μg.mL-1, e uma CFM de 512 a 1.024 μg.mL-1. A substância também inibiu até 92% da formação de biofilme e provocou uma ruptura de até 87% do biofilme pré-formado. Porém, a 2-cloro-N-fenilacetamida não promoveu atividade antifúngica através da ligação ao ergosterol da membrana celular nem prejudicou a integridade da parede celular do fungo. O antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu efeitos antifúngicos significativos inibindo tanto as células planctônicas quanto o biofilme de cepas resistentes ao fluconazol. Vale salientar que sua combinação com outros antifúngicos deve ser evitada e que ainda resta estabelecer seu mecanismo de ação.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBLima, Edeltrudes de Oliveirahttp://lattes.cnpq.br/9406572870167006Guerra, Felipe Queiroga Sarmentohttp://lattes.cnpq.br/4997951182162954Diniz Neto, Hermes2023-01-31T20:44:09Z2022-11-192023-01-31T20:44:09Z2022-10-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/26118porAttribution-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:UFPB2023-05-22T16:32:12Zoai:repositorio.ufpb.br:123456789/26118Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2023-05-22T16:32:12Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol |
title |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol |
spellingShingle |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol Diniz Neto, Hermes Fungicidas 2-cloro-N-fenilacetamida Biofilme Candida spp. Resistência antifúngica Fungicides 2-chloro-N-phenylacetamide Biofilm Antifungal resistance Mecanismo de ação Mechanism of action CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol |
title_full |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol |
title_fullStr |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol |
title_full_unstemmed |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol |
title_sort |
Investigação da atividade antifúngica e anti-biofilme de 2-cloro-n-fenilacetamida sobre Candida albicans e Candida parapsilosis resistentes ao fluconazol |
author |
Diniz Neto, Hermes |
author_facet |
Diniz Neto, Hermes |
author_role |
author |
dc.contributor.none.fl_str_mv |
Lima, Edeltrudes de Oliveira http://lattes.cnpq.br/9406572870167006 Guerra, Felipe Queiroga Sarmento http://lattes.cnpq.br/4997951182162954 |
dc.contributor.author.fl_str_mv |
Diniz Neto, Hermes |
dc.subject.por.fl_str_mv |
Fungicidas 2-cloro-N-fenilacetamida Biofilme Candida spp. Resistência antifúngica Fungicides 2-chloro-N-phenylacetamide Biofilm Antifungal resistance Mecanismo de ação Mechanism of action CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Fungicidas 2-cloro-N-fenilacetamida Biofilme Candida spp. Resistência antifúngica Fungicides 2-chloro-N-phenylacetamide Biofilm Antifungal resistance Mecanismo de ação Mechanism of action CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Infections caused by the Candida genus, especially systemic ones, represent a challenge for public health due to high morbidity and mortality, high associated costs and difficulty in treatment with a good clinical prognosis. Candida albicans is the most frequent cause of this infection, however, the number of cases caused by non-albicans species such as C. parapsilosis has emerged, with a remarkable record of resistant strains. The search for new therapeutic alternatives becomes an important resource in the control of these infections and the use of some already known substances, such as 2-chloro-N-phenylacetamide, is a way to obtain potentially effective new products. Therefore, the antifungal potential of 2-chloro-N-phenylacetamide was investigated against fluconazole-resistant C. albicans and C. parapsilosis strains. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory and fungicidal concentrations (MIC and MFC), inhibition of biofilm formation and its rupture, investigation of the possible mechanism of action, and association between this molecule and amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 μg.mL-1, and a MFC of 512 to 1,024 μg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. However, 2-chloro-N-phenylacetamide did not promote antifungal activity by binding to cell membrane ergosterol, nor did it impair the integrity of the fungal cell wall. Antagonism has been observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal effects by inhibiting both planktonic cells and the biofilm of fluconazole-resistant strains. It is worth noting that its combination with other antifungals should be avoided and that its mechanism of action remains to be established. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11-19 2022-10-21 2023-01-31T20:44:09Z 2023-01-31T20:44:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/26118 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/26118 |
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) instacron:UFPB |
instname_str |
Universidade Federal da Paraíba (UFPB) |
instacron_str |
UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801843004895395840 |