Reposicionamento dos antidepressivos e avaliação da atividade antibacteriana e de nuclease química in vitro de oxalato de escitalopram e clonazepam

Detalhes bibliográficos
Autor(a) principal: Rosa, Taciéli Fagundes da
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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spelling 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
dc.identifier.dark.fl_str_mv ark:/26339/00130000109h6
url 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
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.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
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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