Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
Ano de defesa: | 2018 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
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: |
Análises Clínicas e Toxicológicas
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/20533 |
Resumo: | Rapidly growing mycobacteria (RGM) are opportunistic microorganisms, found in the environment, that can cause both local and disseminated infections. RGM can form structured communities that adhere to solid biotic or abiotic surfaces, characterizing one of their most powerful survival mechanisms, biofilms. Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants such as catheters and prostheses. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with the formation of RGM biofilms. In recent years, the coordination of metals to classic antimicrobials have shown excellent activity against a variety of microorganisms in planktonic form. In this context, this work aimed to evaluate, for the first time, the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) and six clinical isolates of RGM, as well as to evaluate their safe through cytotoxic assays. Different profiles of susceptibility to drugs used in the clinic and to new compounds were determined in our study and in our results it was demonstrated that sulfamethoxazole derivatives complexed with metals showed, in the great majority of cases, activity superior to that of free sulfamethoxazole and other drugs in inhibiting the growth of RGM. The results demonstrate potentiation of the novel compounds in inhibiting the formation and destruction of biofilms of RGM. The antibiofilm activity of gold-complexed sulfamethoxazole, which was able to completely inhibit biofilm formation, is clearly pronounced. In adittion, this compound had the capacity to destroy the biofilm at all concentrations tested. All cytotoxic data are suggestive that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives as well as safe molecules which could be used as potential therapeutic agents for bacterial and biofilm elimination. |
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2021-04-12T17:06:55Z2021-04-12T17:06:55Z2018-03-05http://repositorio.ufsm.br/handle/1/20533Rapidly growing mycobacteria (RGM) are opportunistic microorganisms, found in the environment, that can cause both local and disseminated infections. RGM can form structured communities that adhere to solid biotic or abiotic surfaces, characterizing one of their most powerful survival mechanisms, biofilms. Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants such as catheters and prostheses. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with the formation of RGM biofilms. In recent years, the coordination of metals to classic antimicrobials have shown excellent activity against a variety of microorganisms in planktonic form. In this context, this work aimed to evaluate, for the first time, the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) and six clinical isolates of RGM, as well as to evaluate their safe through cytotoxic assays. Different profiles of susceptibility to drugs used in the clinic and to new compounds were determined in our study and in our results it was demonstrated that sulfamethoxazole derivatives complexed with metals showed, in the great majority of cases, activity superior to that of free sulfamethoxazole and other drugs in inhibiting the growth of RGM. The results demonstrate potentiation of the novel compounds in inhibiting the formation and destruction of biofilms of RGM. The antibiofilm activity of gold-complexed sulfamethoxazole, which was able to completely inhibit biofilm formation, is clearly pronounced. In adittion, this compound had the capacity to destroy the biofilm at all concentrations tested. All cytotoxic data are suggestive that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives as well as safe molecules which could be used as potential therapeutic agents for bacterial and biofilm elimination.Micobactérias de crescimento rápido (MCR) são microrganismos oportunistas, encontrados no ambiente, que podem causar infecções locais e disseminadas. As MCR podem formar comunidades estruturadas, que aderem a superfícies bióticas ou abióticas sólidas, caracterizando um de seus mais poderosos mecanismos de sobrevivência, os biofilmes. Os biofilmes são considerados fontes importantes de infecções em superfícies biomédicas e a maioria das infecções envolvendo formação de biofilmes estão associadas a implantes de dispositivos médicos, como cateteres e próteses. Portanto, existe uma necessidade urgente de novos compostos antimicrobianos que possam combater a resistência microbiana associada à formação de biofilmes de MCR. Nos últimos anos, a coordenação de metais a antimicrobianos clássicos vem demonstrando excelente atividade contra uma variedade de microrganismos na forma planctônica. Sendo assim, este trabalho teve como objetivo avaliar, pela primeira vez, a atividade antibiofilme do sulfametoxazol complexado com Au, Cd, Cu, Ni e Hg frente a Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) e seis isolados clínicos de MCR, bem como avaliar a segurança desses novos compostos através de ensaios citotóxicos. Diferentes perfis de suscetibilidade a fármacos utilizados na clínica e a novos compostos foram determinados em nosso estudo e os resultados demonstraram que os derivados do sulfametoxazol complexados com metais apresentaram, na grande maioria dos casos, atividade superior à do sulfametoxazol livre e outras drogas na inibição do crescimento de MCR. Todos os resultados demonstram a potencialização da atividade dos novos compostos na inibição da formação e destruição de biofilmes de MCR. Destacou-se a atividade antibiofilme do sulfametoxazol complexado com ouro, que foi capaz de inibir completamente a formação de biofilme. Além disso, este composto teve a capacidade de destruir o biofilme em todas as concentrações testadas. Todos os dados citotóxicos são sugestivos de que a maioria dos derivados metálicos do sulfametoxazol são alternativas antimicrobianas, bem como moléculas seguras que podem ser utilizadas como possíveis agentes terapêuticos para a eliminação de bactérias e biofilmes.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilAnálises Clínicas e ToxicológicasAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessMicobactériaBiofilmesResistênciaCompostos inorgânicosMycobacteriaBiofilmsResistenceInorganic compoundsCNPQ::CIENCIAS DA SAUDE::FARMACIAAtividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazolAntimicobacterial and antibiofilm activities and evaluation of in vitro toxicity of sulfamethoxazole metallic complexesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisCampos, Marli Matiko Anraku dehttp://lattes.cnpq.br/6421182991125434Machado, Alencar KolinskiBrucker, Natáliahttp://lattes.cnpq.br/0076452509497790Siqueira, Fallon dos Santos400300000005600ac8e430f-6a47-4d8e-91cd-2fd828e1aa3700fc4879-6054-4f6c-960a-3af159e3e484a0fb3c5d-bcef-417c-8c06-73d8f207ab8c7e1d71bf-4010-48ae-bd49-256dee844c6dreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCF_2018_SIQUEIRA_FALLON.pdfDIS_PPGCF_2018_SIQUEIRA_FALLON.pdfDissertação de Mestradoapplication/pdf2337622http://repositorio.ufsm.br/bitstream/1/20533/1/DIS_PPGCF_2018_SIQUEIRA_FALLON.pdfc8d9abae39523120c9c43e2e6256faf8MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol |
dc.title.alternative.eng.fl_str_mv |
Antimicobacterial and antibiofilm activities and evaluation of in vitro toxicity of sulfamethoxazole metallic complexes |
title |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol |
spellingShingle |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol Siqueira, Fallon dos Santos Micobactéria Biofilmes Resistência Compostos inorgânicos Mycobacteria Biofilms Resistence Inorganic compounds CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol |
title_full |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol |
title_fullStr |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol |
title_full_unstemmed |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol |
title_sort |
Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol |
author |
Siqueira, Fallon dos Santos |
author_facet |
Siqueira, Fallon dos Santos |
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 |
Machado, Alencar Kolinski |
dc.contributor.referee2.fl_str_mv |
Brucker, Natália |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0076452509497790 |
dc.contributor.author.fl_str_mv |
Siqueira, Fallon dos Santos |
contributor_str_mv |
Campos, Marli Matiko Anraku de Machado, Alencar Kolinski Brucker, Natália |
dc.subject.por.fl_str_mv |
Micobactéria Biofilmes Resistência Compostos inorgânicos |
topic |
Micobactéria Biofilmes Resistência Compostos inorgânicos Mycobacteria Biofilms Resistence Inorganic compounds CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Mycobacteria Biofilms Resistence Inorganic compounds |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Rapidly growing mycobacteria (RGM) are opportunistic microorganisms, found in the environment, that can cause both local and disseminated infections. RGM can form structured communities that adhere to solid biotic or abiotic surfaces, characterizing one of their most powerful survival mechanisms, biofilms. Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants such as catheters and prostheses. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with the formation of RGM biofilms. In recent years, the coordination of metals to classic antimicrobials have shown excellent activity against a variety of microorganisms in planktonic form. In this context, this work aimed to evaluate, for the first time, the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) and six clinical isolates of RGM, as well as to evaluate their safe through cytotoxic assays. Different profiles of susceptibility to drugs used in the clinic and to new compounds were determined in our study and in our results it was demonstrated that sulfamethoxazole derivatives complexed with metals showed, in the great majority of cases, activity superior to that of free sulfamethoxazole and other drugs in inhibiting the growth of RGM. The results demonstrate potentiation of the novel compounds in inhibiting the formation and destruction of biofilms of RGM. The antibiofilm activity of gold-complexed sulfamethoxazole, which was able to completely inhibit biofilm formation, is clearly pronounced. In adittion, this compound had the capacity to destroy the biofilm at all concentrations tested. All cytotoxic data are suggestive that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives as well as safe molecules which could be used as potential therapeutic agents for bacterial and biofilm elimination. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-03-05 |
dc.date.accessioned.fl_str_mv |
2021-04-12T17:06:55Z |
dc.date.available.fl_str_mv |
2021-04-12T17:06:55Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/20533 |
url |
http://repositorio.ufsm.br/handle/1/20533 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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400300000005 |
dc.relation.confidence.fl_str_mv |
600 |
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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 |
Análises Clínicas e Toxicológicas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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