Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina
Ano de defesa: | 2012 |
---|---|
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
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/4437 |
Resumo: | The synthesis of compounds that use a nucleoside as the base structure, has an intense field application. Among these compounds, the most known nowadays is azydothymidine or zidovudine, a drug which was first synthesized to work against tumor processes. However, it was discovered that it could take action to viral combat and now it is the drug of choice in the treatment of acquired immunodeficiency syndrome (AIDS). On the other hand, organochalcogens compounds have been calling the attention of the scientific community, mainly because of their potential in biological molecules containing these atoms. Considering this last factor and aiming to explore the structural basis of nucleosides and biological influences that changes in the 5' position of the deoxyribose ring of AZT would promote, it was planned through an efficient and accessible synthetic route to produce a new series of nucleosides, the 5'-arylseleno azidothymidine, which had the insertion of the selenium atom connected to different aril groups. Moreover, the series of selenium derivatives were evaluated for their toxicological potential for oxidative stress (TBARS and thiol peroxidase), where the compounds 5´-p-methylseleno azidothymidine 3b and 5´-p-chloroseleno azidothymidine (3h) had the results of this series, with potential as antioxidant agent. After this, the compounds 3b and 3h were tested against culture cell lines of bladder cancer (5637). The tests aimed to assess the cytotoxicity, cell morphology, apoptosis analysis and gene expression. The results showed that the compounds 3b and 3h present apoptotic profile, additionally they seem to modulate the expression of anti-apoptotic gene. The results obtained indicate that the compounds 3b and 3h in addition of presenting an antioxidant potential, have a pro-apoptotic profile, even more effective than AZT itself. Considering all the results presented, it was concluded that this new nucleoside serie has great antitumor potential and can be used as a chemopreventive, combined to the antioxidant potential. |
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2013-04-302013-04-302012-03-30SOUZA, Diego de. SÍNTESE E ATIVIDADES ANTIOXIDANTE E ANTITUMORAL DE 5´-ARILSELENO AZIDOTIMIDINA. 2012. 190 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/4437The synthesis of compounds that use a nucleoside as the base structure, has an intense field application. Among these compounds, the most known nowadays is azydothymidine or zidovudine, a drug which was first synthesized to work against tumor processes. However, it was discovered that it could take action to viral combat and now it is the drug of choice in the treatment of acquired immunodeficiency syndrome (AIDS). On the other hand, organochalcogens compounds have been calling the attention of the scientific community, mainly because of their potential in biological molecules containing these atoms. Considering this last factor and aiming to explore the structural basis of nucleosides and biological influences that changes in the 5' position of the deoxyribose ring of AZT would promote, it was planned through an efficient and accessible synthetic route to produce a new series of nucleosides, the 5'-arylseleno azidothymidine, which had the insertion of the selenium atom connected to different aril groups. Moreover, the series of selenium derivatives were evaluated for their toxicological potential for oxidative stress (TBARS and thiol peroxidase), where the compounds 5´-p-methylseleno azidothymidine 3b and 5´-p-chloroseleno azidothymidine (3h) had the results of this series, with potential as antioxidant agent. After this, the compounds 3b and 3h were tested against culture cell lines of bladder cancer (5637). The tests aimed to assess the cytotoxicity, cell morphology, apoptosis analysis and gene expression. The results showed that the compounds 3b and 3h present apoptotic profile, additionally they seem to modulate the expression of anti-apoptotic gene. The results obtained indicate that the compounds 3b and 3h in addition of presenting an antioxidant potential, have a pro-apoptotic profile, even more effective than AZT itself. Considering all the results presented, it was concluded that this new nucleoside serie has great antitumor potential and can be used as a chemopreventive, combined to the antioxidant potential.A síntese de compostos que usam como base a estrutura de nucleosídeos é um campo que possui uma intensa aplicação biológica. Dentre estes compostos, o mais conhecido é a azidotimidina ou zidovudina (AZT), um fármaco que teve sua síntese inicial voltada para o combate de processos tumorais. No entanto, descobriu-se que este poderia agir no combate viral e hoje é o fármaco de primeira escolha no tratamento da síndrome da imunodeficiência adquirida. Adicionalmente, compostos organocalcogênio, principalmente compostos de selênio, despertam a atenção da comunidade científica principalmente devido as suas potencialidades biológicas. Dessa forma, a fim de explorar a base estrutural dos nucleosídeos e as influências biológicas que modificações na posição 5´ do anel da desoxirribose do AZT promoveriam, planejou-se através de uma eficiente rota sintética, a síntese de uma nova série de nucleosídeos, os 5´-arilseleno azidotimidina, que apresentaram a inserção do átomo de selênio ligados a diferentes grupamentos arílicos. Com o objetivo de realizarmos uma seleção dos melhores compostos da série de selenonuclesídeos, avaliamos o parâmetro toxicológico para o estresse oxidativo (TBARS e tiol peroxidase) destes compostos. Onde, os compostos 5´-p-metilseleno azidotimidina (3b) e 5´-p-cloroseleno azidotimidina (3h) apresentaram os resultados mais promissores, apresentando inclusive perfil como agente antioxidante. Dessa forma, após realizarmos a triagem, os compostos 3b e 3h tiveram suas atividades testadas frente à cultura celular de linhagem de câncer de bexiga (5637). Os testes buscaram avaliar os parâmetros de citotoxicidade, morfologia celular, análise apoptótica e a expressão gênica. Os resultados obtidos mostraram que os compostos 3b e 3h apresentaram perfil apoptótico, além de serem capazes de modular a expressão do gene anti-apoptótico. Por fim, os resultados obtidos, apontam que os compostos 3b e 3h além de apresentarem um perfil antioxidante, possuem ação pró-apoptótica mais eficientes do que o próprio AZT. Dessa forma, considerando todos os resultados obtidos, foi possível concluir que essa nova série de nucleosídeos apresenta potencial antitumoral, podendo ser usado quimiopreventivamente, aliado ao perfil antioxidante.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaNucleosídeoAZTSelênioAntioxidanteAntitumoralNucleosideAZTSeleniumAntioxidantAntitumorCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICASíntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidinainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisRodrigues, Oscar Endrigo Dorneleshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4763956Z6Alves, Diego da Silvahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4765192T5Dornelles, Lucianohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797177P9Savegnago, Luciellihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4762396U8Schetinger, Maria Rosa Chitolinahttp://lattes.cnpq.br/3561369550388349Souza, Diego de20080000000240050030030050030050009fef019-ac43-4d8b-83d3-3565e4686d7b21f58b3b-e835-4095-825b-5f4eac2422e9afb0358c-5968-4935-9856-009cb2c13f804a671e0c-bfb0-436b-bd8f-ab5645f4229ee562a88b-5d35-4dc2-b392-f3e2cb780dbd98300743-ff68-46b6-b7c0-7145a94b913dinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALSOUZA, DIEGO DE.pdfapplication/pdf6325395http://repositorio.ufsm.br/bitstream/1/4437/1/SOUZA%2c%20DIEGO%20DE.pdf023309b1b09561eccb97e7c13eebdc2dMD51TEXTSOUZA, DIEGO DE.pdf.txtSOUZA, DIEGO DE.pdf.txtExtracted texttext/plain222282http://repositorio.ufsm.br/bitstream/1/4437/2/SOUZA%2c%20DIEGO%20DE.pdf.txt8eb2c06a0240041feed0b1668b2f791bMD52THUMBNAILSOUZA, DIEGO DE.pdf.jpgSOUZA, DIEGO DE.pdf.jpgIM Thumbnailimage/jpeg5834http://repositorio.ufsm.br/bitstream/1/4437/3/SOUZA%2c%20DIEGO%20DE.pdf.jpgfe6003559461255e222433a754722632MD531/44372022-01-05 09:23:23.301oai:repositorio.ufsm.br:1/4437Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-01-05T12:23:23Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina |
title |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina |
spellingShingle |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina Souza, Diego de Nucleosídeo AZT Selênio Antioxidante Antitumoral Nucleoside AZT Selenium Antioxidant Antitumor CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina |
title_full |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina |
title_fullStr |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina |
title_full_unstemmed |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina |
title_sort |
Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina |
author |
Souza, Diego de |
author_facet |
Souza, Diego de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rodrigues, Oscar Endrigo Dorneles |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4763956Z6 |
dc.contributor.referee1.fl_str_mv |
Alves, Diego da Silva |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4765192T5 |
dc.contributor.referee2.fl_str_mv |
Dornelles, Luciano |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797177P9 |
dc.contributor.referee3.fl_str_mv |
Savegnago, Lucielli |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4762396U8 |
dc.contributor.referee4.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3561369550388349 |
dc.contributor.author.fl_str_mv |
Souza, Diego de |
contributor_str_mv |
Rodrigues, Oscar Endrigo Dorneles Alves, Diego da Silva Dornelles, Luciano Savegnago, Lucielli Schetinger, Maria Rosa Chitolina |
dc.subject.por.fl_str_mv |
Nucleosídeo AZT Selênio Antioxidante Antitumoral |
topic |
Nucleosídeo AZT Selênio Antioxidante Antitumoral Nucleoside AZT Selenium Antioxidant Antitumor CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Nucleoside AZT Selenium Antioxidant Antitumor |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The synthesis of compounds that use a nucleoside as the base structure, has an intense field application. Among these compounds, the most known nowadays is azydothymidine or zidovudine, a drug which was first synthesized to work against tumor processes. However, it was discovered that it could take action to viral combat and now it is the drug of choice in the treatment of acquired immunodeficiency syndrome (AIDS). On the other hand, organochalcogens compounds have been calling the attention of the scientific community, mainly because of their potential in biological molecules containing these atoms. Considering this last factor and aiming to explore the structural basis of nucleosides and biological influences that changes in the 5' position of the deoxyribose ring of AZT would promote, it was planned through an efficient and accessible synthetic route to produce a new series of nucleosides, the 5'-arylseleno azidothymidine, which had the insertion of the selenium atom connected to different aril groups. Moreover, the series of selenium derivatives were evaluated for their toxicological potential for oxidative stress (TBARS and thiol peroxidase), where the compounds 5´-p-methylseleno azidothymidine 3b and 5´-p-chloroseleno azidothymidine (3h) had the results of this series, with potential as antioxidant agent. After this, the compounds 3b and 3h were tested against culture cell lines of bladder cancer (5637). The tests aimed to assess the cytotoxicity, cell morphology, apoptosis analysis and gene expression. The results showed that the compounds 3b and 3h present apoptotic profile, additionally they seem to modulate the expression of anti-apoptotic gene. The results obtained indicate that the compounds 3b and 3h in addition of presenting an antioxidant potential, have a pro-apoptotic profile, even more effective than AZT itself. Considering all the results presented, it was concluded that this new nucleoside serie has great antitumor potential and can be used as a chemopreventive, combined to the antioxidant potential. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-03-30 |
dc.date.accessioned.fl_str_mv |
2013-04-30 |
dc.date.available.fl_str_mv |
2013-04-30 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SOUZA, Diego de. SÍNTESE E ATIVIDADES ANTIOXIDANTE E ANTITUMORAL DE 5´-ARILSELENO AZIDOTIMIDINA. 2012. 190 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4437 |
identifier_str_mv |
SOUZA, Diego de. SÍNTESE E ATIVIDADES ANTIOXIDANTE E ANTITUMORAL DE 5´-ARILSELENO AZIDOTIMIDINA. 2012. 190 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
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http://repositorio.ufsm.br/handle/1/4437 |
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por |
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200800000002 |
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Universidade Federal de Santa Maria |
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Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
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UFSM |
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Bioquímica |
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Universidade Federal de Santa Maria |
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