Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg
Ano de defesa: | 2016 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Farmacêuticas
|
Departamento: |
Farmacologia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/17989 |
Resumo: | Mycobacterial infections including Mycobacterium tuberculosis have been increasing globally. The additional prevalence of multidrug-resistant (MDR-TB) strains and extensively drug-resistant tuberculosis (XDR-TB) stimulate an urgent need for the development of new drugs for the treatment of mycobacterial infections. Mycobacteriosis is a type of infection caused by rapidly growing mycobacteria (RGM), which can vary from localized illness, such as skin disease, to disseminated disease. Amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole are antimicrobial drugs chosen to treat such illnesses; however, not all patients obtain the cure. The reason why the treatment does not work for those patients is related to the fact that some clinical strains present resistance to the existing antimicrobial drugs; thereby, the research of new therapeutic approaches is extremely relevant. The coordination of antimicrobial drugs to metals is a promising alternative in the development of effective compounds against resistant microorganisms. Sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against a variety of microorganisms. Considering the importance of fighting against infections associated with RGM, the objective of this study is to evaluate the antimycobacterial activity of metal complexes of sulfonamides against mycobacterials. It determined the minimum inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis and RGM, as well as their interactions with trimethoprim being determined Fractional Inhibitory Concentration Index (FICI) for each association. It also evaluated the action of sulfonamides against biofilms formed by RGM. Sulfonamides showed increased antimicrobial activity when compared to sulfamethoxazole both plantonicas cells and biofilms, and showed synergistic effect when combined with trimethoprim. |
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2019-08-22T11:35:11Z2019-08-22T11:35:11Z2016-07-21http://repositorio.ufsm.br/handle/1/17989Mycobacterial infections including Mycobacterium tuberculosis have been increasing globally. The additional prevalence of multidrug-resistant (MDR-TB) strains and extensively drug-resistant tuberculosis (XDR-TB) stimulate an urgent need for the development of new drugs for the treatment of mycobacterial infections. Mycobacteriosis is a type of infection caused by rapidly growing mycobacteria (RGM), which can vary from localized illness, such as skin disease, to disseminated disease. Amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole are antimicrobial drugs chosen to treat such illnesses; however, not all patients obtain the cure. The reason why the treatment does not work for those patients is related to the fact that some clinical strains present resistance to the existing antimicrobial drugs; thereby, the research of new therapeutic approaches is extremely relevant. The coordination of antimicrobial drugs to metals is a promising alternative in the development of effective compounds against resistant microorganisms. Sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against a variety of microorganisms. Considering the importance of fighting against infections associated with RGM, the objective of this study is to evaluate the antimycobacterial activity of metal complexes of sulfonamides against mycobacterials. It determined the minimum inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis and RGM, as well as their interactions with trimethoprim being determined Fractional Inhibitory Concentration Index (FICI) for each association. It also evaluated the action of sulfonamides against biofilms formed by RGM. Sulfonamides showed increased antimicrobial activity when compared to sulfamethoxazole both plantonicas cells and biofilms, and showed synergistic effect when combined with trimethoprim.Infecções por micobactérias, incluindo Mycobacterium tuberculosis têm vindo a aumentar globalmente. A prevalência de isolados adicionais (MDR-TB) multirresistentes e tuberculose extensivamente resistente (XDR-TB) estimulam uma necessidade urgente para o desenvolvimento de novos fármacos para o tratamento de infecções micobacterianas. Micobactérias de crescimento rápido (MCR) são micro-organismos que podem causar tanto doenças de pele como doença disseminada. Amicacina, cefoxitina, ciprofloxacino, claritromicina, doxiciclina, imipenem e sulfametoxazol são antimicrobianos utilizados para o tratamento de micobacterioses ocasionadas por MCR, porém nem todos os pacientes tratados obtém a cura. Isso ocorre, pois muitos isolados clínicos são resistentes aos antimicrobianos existentes, e, além disso, estes micro-organismos são capazes de formar biofimes. Biofilmes são estruturas capazes de resistir à ação de antimicrobianos e desinfetantes. A dificuldade de tratamento adequado para infecções persistentes, causadas a partir da formação de biofilmes, está diretamente relacionada à estrutura compacta dos mesmos, onde os antimicrobianos convencionais enfrentam dificuldades para penetrar no biofilme. Deste modo, é de extrema relevância a busca por novas opções terapêuticas. Neste contexto, a co-ordenação de antimicrobianos a metais representa uma alternativa promissora na tentativa de encontrar compostos efetivos contra biofilmes. Sulfonamidas complexadas com Au, Cd, Ag, Cu e Hg têm demonstrado ótima atividade frente a uma variedade de micro-organismos, tanto na forma plantônica quanto na forma de biofilme. Tendo em vista a importância em se combater infecções associadas à formação de biofilmes por micobactérias, este trabalho tem como objetivo avaliar a atividade antimicobacteriana de complexos metálicos de sulfonamidas frente às micobacterias. Foi determinada a concentração inibitória mínima (CIM) dos compostos frente a Mycobacterium tuberculosis e MCR, bem como a interação destas com o trimetoprim, sendo determinado o Índice de Concentração Inibitória Fracional (ICIF) para cada associação. Também foi avaliada a ação das sulfonamidas frente a biofilmes formados por MCR. As sulfonamidas apresentaram atividade antimicrobiana aumentada quando comparadas ao sulfametoxazol tanto em células plantonicas quanto em biofilmes, e apresentaram efeito sinérgico quando associadas ao trimetoprim.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessSulfonamidasComplexos metálicosTrimetoprimMicobacteriasSuscetibilidadeBiofilmeSulfonamidesMetal complexesTrimethoprimMycobacterialSusceptibilityBiofilmsCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAAtividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e HgAntimycobacterial activity and antibiofilm of sulfonamides complexed with Au, Cu, Cd, Ag e Hginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCampos, Marli Matiko Anraku dehttp://lattes.cnpq.br/6421182991125434Sato, Daisy Nakamurahttp://lattes.cnpq.br/8176666343767246Botton, Sônia de Avilahttp://lattes.cnpq.br/0814772095155945Vaucher, Rodrigo de Almeidahttp://lattes.cnpq.br/0953074420467371Santos, Roberto Christ Viannahttp://lattes.cnpq.br/9176719594431835http://lattes.cnpq.br/4128871371021894Agertt, Vanessa Albertina201000000000600ac8e430f-6a47-4d8e-91cd-2fd828e1aa377ff973e5-a47b-4af8-bc8f-c1fc75e8995638f13246-060b-4ee6-8c3d-f66d751af64b860bd8db-e3f1-4b8e-bb3e-f1c8f0b143065fdb7e57-59de-4afd-be5f-3f491fff9113c7ae5c41-0a6f-477e-84d0-5e9bb5c89fc4reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCF_2016_AGERTT_VANESSA.pdfTES_PPGCF_2016_AGERTT_VANESSA.pdfTese de Doutoradoapplication/pdf1420812http://repositorio.ufsm.br/bitstream/1/17989/1/TES_PPGCF_2016_AGERTT_VANESSA.pdf98c65e77262598e5035376c926d9751bMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg |
dc.title.alternative.eng.fl_str_mv |
Antimycobacterial activity and antibiofilm of sulfonamides complexed with Au, Cu, Cd, Ag e Hg |
title |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg |
spellingShingle |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg Agertt, Vanessa Albertina Sulfonamidas Complexos metálicos Trimetoprim Micobacterias Suscetibilidade Biofilme Sulfonamides Metal complexes Trimethoprim Mycobacterial Susceptibility Biofilms CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg |
title_full |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg |
title_fullStr |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg |
title_full_unstemmed |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg |
title_sort |
Atividade antimicobacteriana e antibiofilme de sulfonamidas complexadas com Au, Cu, Cd, Ag e Hg |
author |
Agertt, Vanessa Albertina |
author_facet |
Agertt, Vanessa Albertina |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Campos, Marli Matiko Anraku de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6421182991125434 |
dc.contributor.referee1.fl_str_mv |
Sato, Daisy Nakamura |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/8176666343767246 |
dc.contributor.referee2.fl_str_mv |
Botton, Sônia de Avila |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0814772095155945 |
dc.contributor.referee3.fl_str_mv |
Vaucher, Rodrigo de Almeida |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/0953074420467371 |
dc.contributor.referee4.fl_str_mv |
Santos, Roberto Christ Vianna |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/9176719594431835 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4128871371021894 |
dc.contributor.author.fl_str_mv |
Agertt, Vanessa Albertina |
contributor_str_mv |
Campos, Marli Matiko Anraku de Sato, Daisy Nakamura Botton, Sônia de Avila Vaucher, Rodrigo de Almeida Santos, Roberto Christ Vianna |
dc.subject.por.fl_str_mv |
Sulfonamidas Complexos metálicos Trimetoprim Micobacterias Suscetibilidade Biofilme Sulfonamides |
topic |
Sulfonamidas Complexos metálicos Trimetoprim Micobacterias Suscetibilidade Biofilme Sulfonamides Metal complexes Trimethoprim Mycobacterial Susceptibility Biofilms CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Metal complexes Trimethoprim Mycobacterial Susceptibility Biofilms |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Mycobacterial infections including Mycobacterium tuberculosis have been increasing globally. The additional prevalence of multidrug-resistant (MDR-TB) strains and extensively drug-resistant tuberculosis (XDR-TB) stimulate an urgent need for the development of new drugs for the treatment of mycobacterial infections. Mycobacteriosis is a type of infection caused by rapidly growing mycobacteria (RGM), which can vary from localized illness, such as skin disease, to disseminated disease. Amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole are antimicrobial drugs chosen to treat such illnesses; however, not all patients obtain the cure. The reason why the treatment does not work for those patients is related to the fact that some clinical strains present resistance to the existing antimicrobial drugs; thereby, the research of new therapeutic approaches is extremely relevant. The coordination of antimicrobial drugs to metals is a promising alternative in the development of effective compounds against resistant microorganisms. Sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against a variety of microorganisms. Considering the importance of fighting against infections associated with RGM, the objective of this study is to evaluate the antimycobacterial activity of metal complexes of sulfonamides against mycobacterials. It determined the minimum inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis and RGM, as well as their interactions with trimethoprim being determined Fractional Inhibitory Concentration Index (FICI) for each association. It also evaluated the action of sulfonamides against biofilms formed by RGM. Sulfonamides showed increased antimicrobial activity when compared to sulfamethoxazole both plantonicas cells and biofilms, and showed synergistic effect when combined with trimethoprim. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-07-21 |
dc.date.accessioned.fl_str_mv |
2019-08-22T11:35:11Z |
dc.date.available.fl_str_mv |
2019-08-22T11:35:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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http://repositorio.ufsm.br/handle/1/17989 |
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http://repositorio.ufsm.br/handle/1/17989 |
dc.language.iso.fl_str_mv |
por |
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por |
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201000000000 |
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600 |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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