Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/00130000109h6 |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21605 |
Resumo: | The emergence of multiresistance to commercially available antimicrobials today is likely to continue to be one of the major global public health problems, as it has worrying clinical and economic consequences. Concomitant with the increase in infections caused by multidrugresistant microorganisms (MDR), there has been a drastic reduction of new antibacterials in the market, as well as investments for their creation. In addition to antimicrobial resistance, resistance to antitumor drugs is already a reality. Thus, it is essential to search for new substances and / or compounds that exhibit antibacterial and / or antitumor activity. With this, drug repositioning has emerged as an alternative approach for the faster identification of effective drugs. In this sense, the present study aimed, in the first article, to present to the scientific community the current research on the repositioning of antidepressants for the treatment of infections caused by microorganisms. In the second manuscript, the individual antibacterial activity and in combination with antibacterials of the non-antibiotics escitalopram oxalate and clonazepam were analyzed against standard strains and clinical isolates multiresistant. In addition, the chemical nuclease ability of these drugs was analyzed. In the first article, we report that antidepressant drugs, highlighting the class of selective serotonin reuptake inhibitors (SSRIs), have significant activity against several microorganisms. We present 14 studies covering the repositioning of antidepressant drugs to treat infections. Among the antidepressants, escitalopram oxalate was reported with activity reported in vitro against standard bacterial strains. In the second manuscript, we report the antibacterial and chemical nuclease activity of the drugs oxalate of escitalopram and clonazepam. The first was active against a standard Gram-negative strain and eight Grampositive MDR clinical isolates. The second drug showed activity against both Gram-positive and Gram-negative, with four standard Gram-positive strains and all Gram-positive and Gram-negative MDR clinical isolates. Escitalopram oxalate and clonazepam showed activity in vitro when individually associated with ciprofloxacin and sulfamethoxazole-trimethoprim against standard strains and clinical MDR Gram-positive isolates. Clonazepam was also active against a gram-negative bacterium. Clonazepam was able to cleave the plasmidial DNA. Further studies should be performed by our research group, in order to verify the activity of clonazepam against tumor cell lines. Therefore, in this work we show that these two drugs constitute a promising alternative to redirection in the treatment of infectious diseases and also for neoplasias. Further studies, using different techniques, are needed to elucidate the mechanisms of action involved. |
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Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepamRepositioning antidepressives and evaluating the antibacterial and in vitro chemical nuclease activity of escitalopram oxalate and clonazepamReposicionamento de medicamentosClivagem do DNAAntidepressivosOxalato de escitalopramClonazepamDrug repositioningDNA cleavageAntidepressive agentsEscitalopram oxalateCNPQ::CIENCIAS DA SAUDE::FARMACIAThe emergence of multiresistance to commercially available antimicrobials today is likely to continue to be one of the major global public health problems, as it has worrying clinical and economic consequences. Concomitant with the increase in infections caused by multidrugresistant microorganisms (MDR), there has been a drastic reduction of new antibacterials in the market, as well as investments for their creation. In addition to antimicrobial resistance, resistance to antitumor drugs is already a reality. Thus, it is essential to search for new substances and / or compounds that exhibit antibacterial and / or antitumor activity. With this, drug repositioning has emerged as an alternative approach for the faster identification of effective drugs. In this sense, the present study aimed, in the first article, to present to the scientific community the current research on the repositioning of antidepressants for the treatment of infections caused by microorganisms. In the second manuscript, the individual antibacterial activity and in combination with antibacterials of the non-antibiotics escitalopram oxalate and clonazepam were analyzed against standard strains and clinical isolates multiresistant. In addition, the chemical nuclease ability of these drugs was analyzed. In the first article, we report that antidepressant drugs, highlighting the class of selective serotonin reuptake inhibitors (SSRIs), have significant activity against several microorganisms. We present 14 studies covering the repositioning of antidepressant drugs to treat infections. Among the antidepressants, escitalopram oxalate was reported with activity reported in vitro against standard bacterial strains. In the second manuscript, we report the antibacterial and chemical nuclease activity of the drugs oxalate of escitalopram and clonazepam. The first was active against a standard Gram-negative strain and eight Grampositive MDR clinical isolates. The second drug showed activity against both Gram-positive and Gram-negative, with four standard Gram-positive strains and all Gram-positive and Gram-negative MDR clinical isolates. Escitalopram oxalate and clonazepam showed activity in vitro when individually associated with ciprofloxacin and sulfamethoxazole-trimethoprim against standard strains and clinical MDR Gram-positive isolates. Clonazepam was also active against a gram-negative bacterium. Clonazepam was able to cleave the plasmidial DNA. Further studies should be performed by our research group, in order to verify the activity of clonazepam against tumor cell lines. Therefore, in this work we show that these two drugs constitute a promising alternative to redirection in the treatment of infectious diseases and also for neoplasias. Further studies, using different techniques, are needed to elucidate the mechanisms of action involved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA emergência da multirresistência aos antimicrobianos disponíveis comercialmente na atualidade é provavelmente e continuará a ser um dos grandes problemas de saúde pública mundial, dado que apresenta consequências clínicas e econômicas preocupantes. Concomitante ao aumento das infecções ocasionadas por microrganismos resistentes a múltiplas drogas (MDR) ocorreu uma redução drástica de novos antibacterianos no mercado, bem como, investimentos para sua criação. Além da resistência aos antimicrobianos, a resistência aos medicamentos antitumorais também já é uma realidade. Assim, é essencial a pesquisa de novas substâncias e/ou compostos que apresentem atividade antibacteriana e/ou antitumoral. Com isso, o reposicionamento de fármacos surgiu como uma abordagem alternativa para a identificação mais rápida de medicamentos eficazes. Nesse sentido, o presente estudo objetivou, no primeiro artigo, apresentar à comunidade científica a pesquisa atual do reposicionamento de antidepressivos para o tratamento de infecções ocasionadas por microrganismos. No segundo manuscrito, analisou-se a atividade antibacteriana individual e em combinação com antibacterianos dos não-antibióticos oxalato de escitalopram e clonazepam frente a cepas padrão e isolados clínicos multirresistentes. Além disso, foi analisada a capacidade de nuclease química desses medicamentos. No primeiro artigo, relatamos que medicamentos antidepressivos, destacando a classe dos inibidores seletivos da recaptação da serotonina (ISRSs), apresentam atividade significativa contra vários microrganismos. Foram apresentados 14 estudos abrangendo o reposicionamento de medicamentos antidepressivos para tratamento de infecções. Dentre os antidepressivos, foi citado o oxalato de escitalopram com atividade relatada in vitro frente a cepas bacterianas padrão. No segundo manuscrito, relatamos a atividade antibacteriana e de nuclease química dos medicamentos oxalato de escitalopram e clonazepam. O primeiro foi ativo frente a uma cepa padrão Gram-negativa e oito isolados clínicos MDR Gram-positivos. O segundo medicamento apresentou atividade tanto frente a Gram-positivas quanto a Gram-negativas, sendo quatro cepas padrão Gram-positivas e todos os isolados clínicos MDR Gram-positivos e Gram-negativos. Oxalato de escitalopram e clonazepam apresentaram atividade in vitro quando associados, individualmente, com ciprofloxacino e sulfametoxazol-trimetoprima frente a cepas-padrão e isolados clínicos MDR Gram-positivos. O clonazepam também foi ativo frente a uma bactéria Gram-negativa. Clonazepam foi capaz de clivar o DNA plasmidial. Mais estudos devem ser realizados pelo nosso grupo de pesquisa, com objetivo de verificar a atividade do clonazepam frente a linhagens celulares tumorais. Portanto, nesse trabalho evidenciamos que estes dois medicamentos constituem uma alternativa promissora ao redirecionamento no tratamento de doenças infecciosas e também para neoplasias. São necessários estudos adicionais, utilizando diferentes técnicas, para a elucidação dos mecanismos de ação envolvidos.Universidade Federal de Santa MariaBrasilAnálises Clínicas e ToxicológicasUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeHorner, Rosmarihttp://lattes.cnpq.br/5907084134183708Ramos, Daniela FernandesCóser, Virgínia MariaRosa, Taciéli Fagundes da2021-07-27T11:37:36Z2021-07-27T11:37:36Z2019-08-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/21605ark:/26339/00130000109h6porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-10-06T19:55:57Zoai:repositorio.ufsm.br:1/21605Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-06T19:55:57Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam Repositioning antidepressives and evaluating the antibacterial and in vitro chemical nuclease activity of escitalopram oxalate and clonazepam |
title |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam |
spellingShingle |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam Rosa, Taciéli Fagundes da Reposicionamento de medicamentos Clivagem do DNA Antidepressivos Oxalato de escitalopram Clonazepam Drug repositioning DNA cleavage Antidepressive agents Escitalopram oxalate CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam |
title_full |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam |
title_fullStr |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam |
title_full_unstemmed |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam |
title_sort |
Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam |
author |
Rosa, Taciéli Fagundes da |
author_facet |
Rosa, Taciéli Fagundes da |
author_role |
author |
dc.contributor.none.fl_str_mv |
Horner, Rosmari http://lattes.cnpq.br/5907084134183708 Ramos, Daniela Fernandes Cóser, Virgínia Maria |
dc.contributor.author.fl_str_mv |
Rosa, Taciéli Fagundes da |
dc.subject.por.fl_str_mv |
Reposicionamento de medicamentos Clivagem do DNA Antidepressivos Oxalato de escitalopram Clonazepam Drug repositioning DNA cleavage Antidepressive agents Escitalopram oxalate CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Reposicionamento de medicamentos Clivagem do DNA Antidepressivos Oxalato de escitalopram Clonazepam Drug repositioning DNA cleavage Antidepressive agents Escitalopram oxalate CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
The emergence of multiresistance to commercially available antimicrobials today is likely to continue to be one of the major global public health problems, as it has worrying clinical and economic consequences. Concomitant with the increase in infections caused by multidrugresistant microorganisms (MDR), there has been a drastic reduction of new antibacterials in the market, as well as investments for their creation. In addition to antimicrobial resistance, resistance to antitumor drugs is already a reality. Thus, it is essential to search for new substances and / or compounds that exhibit antibacterial and / or antitumor activity. With this, drug repositioning has emerged as an alternative approach for the faster identification of effective drugs. In this sense, the present study aimed, in the first article, to present to the scientific community the current research on the repositioning of antidepressants for the treatment of infections caused by microorganisms. In the second manuscript, the individual antibacterial activity and in combination with antibacterials of the non-antibiotics escitalopram oxalate and clonazepam were analyzed against standard strains and clinical isolates multiresistant. In addition, the chemical nuclease ability of these drugs was analyzed. In the first article, we report that antidepressant drugs, highlighting the class of selective serotonin reuptake inhibitors (SSRIs), have significant activity against several microorganisms. We present 14 studies covering the repositioning of antidepressant drugs to treat infections. Among the antidepressants, escitalopram oxalate was reported with activity reported in vitro against standard bacterial strains. In the second manuscript, we report the antibacterial and chemical nuclease activity of the drugs oxalate of escitalopram and clonazepam. The first was active against a standard Gram-negative strain and eight Grampositive MDR clinical isolates. The second drug showed activity against both Gram-positive and Gram-negative, with four standard Gram-positive strains and all Gram-positive and Gram-negative MDR clinical isolates. Escitalopram oxalate and clonazepam showed activity in vitro when individually associated with ciprofloxacin and sulfamethoxazole-trimethoprim against standard strains and clinical MDR Gram-positive isolates. Clonazepam was also active against a gram-negative bacterium. Clonazepam was able to cleave the plasmidial DNA. Further studies should be performed by our research group, in order to verify the activity of clonazepam against tumor cell lines. Therefore, in this work we show that these two drugs constitute a promising alternative to redirection in the treatment of infectious diseases and also for neoplasias. Further studies, using different techniques, are needed to elucidate the mechanisms of action involved. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-08-22 2021-07-27T11:37:36Z 2021-07-27T11:37:36Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21605 |
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ark:/26339/00130000109h6 |
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http://repositorio.ufsm.br/handle/1/21605 |
identifier_str_mv |
ark:/26339/00130000109h6 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Análises Clínicas e Toxicológicas UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Análises Clínicas e Toxicológicas UFSM Programa de Pós-Graduação em Ciências Farmacêuticas 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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Universidade Federal de Santa Maria (UFSM) |
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UFSM |
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UFSM |
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Manancial - Repositório Digital da UFSM |
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Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
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atendimento.sib@ufsm.br||tedebc@gmail.com |
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