Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório

Detalhes bibliográficos
Autor(a) principal: Cortés, Margarita Alexandra Peña
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/8898
Resumo: Respiratory syncytial virus (RSV) is a highly contagious viral agent and the most common respiratory diseases of lower tract being one of the major causes of morbidity and mortality in children, elderly and immunocompromised. Treatment includes supportive therapy and ribavirin. However, antiviral therapies are expensive, difficult to administer and are not proven to be effective. The aim of this study was to investigate in vitro the antiviral activity of three azo compounds synthesized from the structural alteration of the modified resveratrol stilbene in MRC-5 and A549 cells against RSV infection. The effect of compounds REDRESV 01, REDRESV 02 and REDRESV 03 on cell viability, inhibitory concentration, cytopathic reduction activity and virucidal activity were evaluated by MTT assay. Data showed that REDRESV 01 is cytotoxic for both cell lines showing IC50 58.6μM (MRC-5) and 17.43μM (A549). The study was followed only with the compounds REDRESV 02 (MRC-5 = 87.58μM and A549 = 40.73μM) and REDRESV 03 (MRC-5 = 150.1μM and A549 = 43.44μM) because of the higher IC50 values. Data indicated that the low percentages of inhibition on viral replication were not promising in the search for new antiviral drugs since compounds tested were not able to maintain a significantly viable number of cells during infection. However, in post-infection treatment REDRESV 02 and REDRESV 03 showed selectivity at concentration of 20 μM for the tumor cell (A549) when infected. Both compounds decreased viability twice of the infected A549 cell as compared to the viral control. Compounds also showed a possible virucidal activity which may indicate besides having a cytotoxic effect on tumor cells they may still inactivate the circulating particles when cells are infected. Although the compounds have shown promising results for the treatment of cancer patients infected with RSV new studies should be conducted to investigate other types of virus and other types of cancer, as well as the mechanisms involved in this process.
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spelling Souto, André Arigonyhttp://lattes.cnpq.br/9694457902995525Cortés, Margarita Alexandra Peña2019-09-30T13:24:41Z2017-03-13http://tede2.pucrs.br/tede2/handle/tede/8898Respiratory syncytial virus (RSV) is a highly contagious viral agent and the most common respiratory diseases of lower tract being one of the major causes of morbidity and mortality in children, elderly and immunocompromised. Treatment includes supportive therapy and ribavirin. However, antiviral therapies are expensive, difficult to administer and are not proven to be effective. The aim of this study was to investigate in vitro the antiviral activity of three azo compounds synthesized from the structural alteration of the modified resveratrol stilbene in MRC-5 and A549 cells against RSV infection. The effect of compounds REDRESV 01, REDRESV 02 and REDRESV 03 on cell viability, inhibitory concentration, cytopathic reduction activity and virucidal activity were evaluated by MTT assay. Data showed that REDRESV 01 is cytotoxic for both cell lines showing IC50 58.6μM (MRC-5) and 17.43μM (A549). The study was followed only with the compounds REDRESV 02 (MRC-5 = 87.58μM and A549 = 40.73μM) and REDRESV 03 (MRC-5 = 150.1μM and A549 = 43.44μM) because of the higher IC50 values. Data indicated that the low percentages of inhibition on viral replication were not promising in the search for new antiviral drugs since compounds tested were not able to maintain a significantly viable number of cells during infection. However, in post-infection treatment REDRESV 02 and REDRESV 03 showed selectivity at concentration of 20 μM for the tumor cell (A549) when infected. Both compounds decreased viability twice of the infected A549 cell as compared to the viral control. Compounds also showed a possible virucidal activity which may indicate besides having a cytotoxic effect on tumor cells they may still inactivate the circulating particles when cells are infected. Although the compounds have shown promising results for the treatment of cancer patients infected with RSV new studies should be conducted to investigate other types of virus and other types of cancer, as well as the mechanisms involved in this process.O vírus sincicial respiratório (VSR) é um agente viral altamente contagioso e o mais comum nas doenças respiratórias do trato inferior sendo uma das maiores causas de morbidade e mortalidade em crianças, idosos e imunodeprimidos. O tratamento inclui terapia de suporte e ribavirina. Contudo, as terapias antivirais são caras, difíceis de administrar e não são comprovadamente eficazes. O objetivo deste estudo foi investigar in vitro a atividade antiviral de três azocompostos sintetizados a partir da alteração estrutural do estilbeno modificado do resveratrol em células MRC-5 e A549 frente à infecção pelo VSR. Foram avaliados o efeito sobre a viabilidade celular, a concentração inibitória, a redução do efeito citopático e o efeito virucida dos compostos REDRESV 01, REDRESV 02 e REDRESV 03 utilizando-se a técnica de MTT. Os dados mostraram que REDRESV 01 é mais citotóxico para as duas linhagens apresentando IC50 58,6μM (MRC-5) e 17,43μM (A549). Por apresentarem valores de IC50 maiores seguiu-se o estudo apenas com os compostos REDRESV 02 (MRC-5 = 87,58μM e A549 = 40,73μM) e REDRESV 03 (MRC-5 = 150,1μM e A549 = 43,44μM). Os resultados indicaram que as baixas porcentagens de inibição da replicação viral pelos compostos testados não foram promissoras na pesquisa de novos fármacos antivirais uma vez que estes não foram capazes de manter um número significativamente viável de células durante a infecção. No entanto, no tratamento pós-infecção os compostos REDRESV 02 e REDRESV 03 mostraram seletividade na concentração de 20μM para a célula tumoral (A549) quando infectada. Os dois compostos diminuíram cerca de duas vezes mais a viabilidade da célula A549 infectada quando comparados com o controle viral. Os compostos também mostraram um possível efeito virucida o que pode ser um indicativo que além destes terem um efeito citotóxico para as células tumorais eles ainda podem inativar as partículas circulantes quando estas células estiverem infectadas. Apesar dos compostos terem apresentado resultados promissores para o tratamento de pacientes oncológicos infectados com VSR novos estudos devem ser realizados para investigar outros tipos de vírus e outros tipos de câncer, bem como, os mecanismos envolvidos nesse processo.Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2019-09-17T17:41:50Z No. of bitstreams: 1 MARGARITA_ALEXANDRA_PEÑA_CORTES_DIS.pdf: 2046854 bytes, checksum: fb3a44a13ac417d09b8052e6b6a5e778 (MD5)Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2019-09-30T13:18:19Z (GMT) No. of bitstreams: 1 MARGARITA_ALEXANDRA_PEÑA_CORTES_DIS.pdf: 2046854 bytes, checksum: fb3a44a13ac417d09b8052e6b6a5e778 (MD5)Made available in DSpace on 2019-09-30T13:24:41Z (GMT). No. of bitstreams: 1 MARGARITA_ALEXANDRA_PEÑA_CORTES_DIS.pdf: 2046854 bytes, checksum: fb3a44a13ac417d09b8052e6b6a5e778 (MD5) Previous issue date: 2017-03-13Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/176478/DIS_MARGARITA_ALEXANDRA_PENA_CORTES_CONFIDENCIAL.pdf.jpghttp://tede2.pucrs.br:80/tede2/retrieve/178272/DIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Biologia Celular e MolecularPUCRSBrasilEscola de CiênciasAzo CompostosVírus Sincicial RespiratórioAtividade AntiviralDoença do Trato Respiratório InferiorCâncer de PulmãoCIENCIAS BIOLOGICAS::BIOLOGIA GERALAnálise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratórioinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTrabalho será publicado como artigo ou livro06 meses30/03/20203463594373552466096500500600-16345593859312446973590462550136975366info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSORIGINALDIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdfDIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdfapplication/pdf2046854http://tede2.pucrs.br/tede2/bitstream/tede/8898/5/DIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdffb3a44a13ac417d09b8052e6b6a5e778MD55THUMBNAILDIS_MARGARITA_ALEXANDRA_PENA_CORTES_CONFIDENCIAL.pdf.jpgDIS_MARGARITA_ALEXANDRA_PENA_CORTES_CONFIDENCIAL.pdf.jpgimage/jpeg4084http://tede2.pucrs.br/tede2/bitstream/tede/8898/4/DIS_MARGARITA_ALEXANDRA_PENA_CORTES_CONFIDENCIAL.pdf.jpg10e423e605bb5da20fe67f8d975a4464MD54DIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdf.jpgDIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdf.jpgimage/jpeg5774http://tede2.pucrs.br/tede2/bitstream/tede/8898/7/DIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdf.jpg79678fe1c51818d27a92fd8c55a6cde2MD57TEXTDIS_MARGARITA_ALEXANDRA_PENA_CORTES_CONFIDENCIAL.pdf.txtDIS_MARGARITA_ALEXANDRA_PENA_CORTES_CONFIDENCIAL.pdf.txttext/plain2015http://tede2.pucrs.br/tede2/bitstream/tede/8898/3/DIS_MARGARITA_ALEXANDRA_PENA_CORTES_CONFIDENCIAL.pdf.txt3368470cb8de2892b1e066612455b3bcMD53DIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdf.txtDIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdf.txttext/plain117123http://tede2.pucrs.br/tede2/bitstream/tede/8898/6/DIS_MARGARITA_ALEXANDRA_PENA_CORTES_COMPLETO.pdf.txtabb5e3ec4bc07023dae1a41e74a5f0d2MD56LICENSElicense.txtlicense.txttext/plain; charset=utf-8590http://tede2.pucrs.br/tede2/bitstream/tede/8898/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/88982020-07-13 20:00:52.656oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2020-07-13T23:00:52Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false
dc.title.por.fl_str_mv Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
title Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
spellingShingle Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
Cortés, Margarita Alexandra Peña
Azo Compostos
Vírus Sincicial Respiratório
Atividade Antiviral
Doença do Trato Respiratório Inferior
Câncer de Pulmão
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
title_short Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
title_full Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
title_fullStr Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
title_full_unstemmed Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
title_sort Análise da capacidade antiviral de azoestilbenoides frente ao vírus sindical respiratório
author Cortés, Margarita Alexandra Peña
author_facet Cortés, Margarita Alexandra Peña
author_role author
dc.contributor.advisor1.fl_str_mv Souto, André Arigony
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9694457902995525
dc.contributor.author.fl_str_mv Cortés, Margarita Alexandra Peña
contributor_str_mv Souto, André Arigony
dc.subject.por.fl_str_mv Azo Compostos
Vírus Sincicial Respiratório
Atividade Antiviral
Doença do Trato Respiratório Inferior
Câncer de Pulmão
topic Azo Compostos
Vírus Sincicial Respiratório
Atividade Antiviral
Doença do Trato Respiratório Inferior
Câncer de Pulmão
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
description Respiratory syncytial virus (RSV) is a highly contagious viral agent and the most common respiratory diseases of lower tract being one of the major causes of morbidity and mortality in children, elderly and immunocompromised. Treatment includes supportive therapy and ribavirin. However, antiviral therapies are expensive, difficult to administer and are not proven to be effective. The aim of this study was to investigate in vitro the antiviral activity of three azo compounds synthesized from the structural alteration of the modified resveratrol stilbene in MRC-5 and A549 cells against RSV infection. The effect of compounds REDRESV 01, REDRESV 02 and REDRESV 03 on cell viability, inhibitory concentration, cytopathic reduction activity and virucidal activity were evaluated by MTT assay. Data showed that REDRESV 01 is cytotoxic for both cell lines showing IC50 58.6μM (MRC-5) and 17.43μM (A549). The study was followed only with the compounds REDRESV 02 (MRC-5 = 87.58μM and A549 = 40.73μM) and REDRESV 03 (MRC-5 = 150.1μM and A549 = 43.44μM) because of the higher IC50 values. Data indicated that the low percentages of inhibition on viral replication were not promising in the search for new antiviral drugs since compounds tested were not able to maintain a significantly viable number of cells during infection. However, in post-infection treatment REDRESV 02 and REDRESV 03 showed selectivity at concentration of 20 μM for the tumor cell (A549) when infected. Both compounds decreased viability twice of the infected A549 cell as compared to the viral control. Compounds also showed a possible virucidal activity which may indicate besides having a cytotoxic effect on tumor cells they may still inactivate the circulating particles when cells are infected. Although the compounds have shown promising results for the treatment of cancer patients infected with RSV new studies should be conducted to investigate other types of virus and other types of cancer, as well as the mechanisms involved in this process.
publishDate 2017
dc.date.issued.fl_str_mv 2017-03-13
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dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Biologia Celular e Molecular
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