Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2
Ano de defesa: | 2023 |
---|---|
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
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química
|
Departamento: |
Química
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/29622 |
Resumo: | In this work, a reaction protocol was developed for a new class of pseudo-peptides through multicomponent reactions (MCR) of the Ugi’s four component reaction (U-4CR) type, starting from chalcogenonucleosides. The synthetic route was planned to have a single reaction step under mild conditions. The U-4CR reactions provide great structural versatility since the four components presented groups that could be modified: amine, aldehyde, carboxylic acid, and isocyanide. This study emphasized the amine component, in which 5'-arylchalcogenyl-3-amino-thymidines 5a-f were employed. The carboxylic acid component was also explored, two types of isocyanates were studied, and only one aldehyde was used in the reactions. The synthetic route involved a one-pot reaction at room temperature using an ethanolic milieu, and the 9a-q products were obtained with yields ranging from 25 to 77%. The products were characterized by 1H and 13C NMR spectroscopy, and also HRMS. Two-dimensional 1H and 13C NMR experiments were carried out, however, the registered spectra exhibited poor resolution and no signal attribution was performed. In silico molecular docking studies were performed to evaluate the possible interactions between the obtained compounds and the main protease (Mpro) of SARS-CoV-2. The seventeen compounds were evaluated, and nine compounds exhibited favorable interactions at the stable position close to the active site of the Mpro of SARS-CoV-2, with a highlight for compounds 9b and 9h, whose binding energies with Mpro are -8.7 and -8.8 kcal mol-1, respectively, which are bigger than the exhibit by the standard drug nirmatrelvir. In concluding remarks, seventeen new molecules were synthesized in good yields, making clear the success of Ugi 4-CR reactions in forming pseudo-peptides using chalcogenonucleosides. As prospects for further studies, these molecules can be important targets for investigating biological activities, such as evaluating antitumor activity, among others. |
id |
UFSM_76e2af72a42b126b21c5792f2f1e2323 |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/29622 |
network_acronym_str |
UFSM |
network_name_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
repository_id_str |
|
spelling |
2023-07-04T13:28:51Z2023-07-04T13:28:51Z2023-03-30http://repositorio.ufsm.br/handle/1/29622In this work, a reaction protocol was developed for a new class of pseudo-peptides through multicomponent reactions (MCR) of the Ugi’s four component reaction (U-4CR) type, starting from chalcogenonucleosides. The synthetic route was planned to have a single reaction step under mild conditions. The U-4CR reactions provide great structural versatility since the four components presented groups that could be modified: amine, aldehyde, carboxylic acid, and isocyanide. This study emphasized the amine component, in which 5'-arylchalcogenyl-3-amino-thymidines 5a-f were employed. The carboxylic acid component was also explored, two types of isocyanates were studied, and only one aldehyde was used in the reactions. The synthetic route involved a one-pot reaction at room temperature using an ethanolic milieu, and the 9a-q products were obtained with yields ranging from 25 to 77%. The products were characterized by 1H and 13C NMR spectroscopy, and also HRMS. Two-dimensional 1H and 13C NMR experiments were carried out, however, the registered spectra exhibited poor resolution and no signal attribution was performed. In silico molecular docking studies were performed to evaluate the possible interactions between the obtained compounds and the main protease (Mpro) of SARS-CoV-2. The seventeen compounds were evaluated, and nine compounds exhibited favorable interactions at the stable position close to the active site of the Mpro of SARS-CoV-2, with a highlight for compounds 9b and 9h, whose binding energies with Mpro are -8.7 and -8.8 kcal mol-1, respectively, which are bigger than the exhibit by the standard drug nirmatrelvir. In concluding remarks, seventeen new molecules were synthesized in good yields, making clear the success of Ugi 4-CR reactions in forming pseudo-peptides using chalcogenonucleosides. As prospects for further studies, these molecules can be important targets for investigating biological activities, such as evaluating antitumor activity, among others.Nesse trabalho, desenvolveu-se um protocolo reacional para uma nova classe de pseudo-peptídeos, através das reações multicomponentes (MCR) do tipo Ugi de quatro componentes (U-4CR), a partir de calcogenonucleosídeos. Planejou-se a elaboração de uma rota sintética envolvendo transformações simples, em condições reacionais brandas e, em uma única etapa reacional. As reações multicomponentes de Ugi possuem uma grande versatilidade estrutural, uma vez que, os quatro componentes das reações de Ugi apresentaram grupamentos passíveis de modificações: amina, aldeído, ácido carboxílico e, isocianeto. Este estudo direcionou a ênfase para o componente amina, no qual foram empregadas as 5’-arilcalcogenil-3-amino-timidinas 5a-f. O componente ácido carboxílico também foi explorado, dois tipos de isocianetos foram estudados e apenas um aldeído foi empregado nas reações. O roteiro de síntese desenvolvido envolveu uma reação one-pot à temperatura ambiente, em meio etanólico, e os produtos 9a-q foram obtidos com valores de rendimentos na faixa de 25 a 77%. Os produtos foram caracterizados por RMN de 1H e de 13C e EMAR. Foram realizados experimentos de RMN de 1H e 13C em duas dimensões, no entanto, os espectros registrados não apresentaram resolução suficiente para fazer qualquer atribuição aos sinais. Também foram avaliados estudos de ancoragem molecular in silico para prever as possíveis interações entre os compostos obtidos e a protease principal (Mpro) do SARS-CoV-2. Os dezessete compostos foram avaliados, e 9 compostos apresentaram interações favoráveis na posição mais estável na região do sítio ativo da Mpro do SARS-CoV-2, com destaque para os compostos 9b e 9h, cujos valores para a energia de ligação com a Mpro são de –8,7 e –8,8 kcal mol-1, respectivamente, no qual se mostraram superiores ao fármaco utilizado como padrão nirmatrelvir. Ao final deste trabalho, foram sintetizadas 17 novas moléculas, em bons rendimentos, deixando claro o sucesso das U-4CR na formação de pseudo-peptídeos utilizando calcogenonucleosídeos. Como perspectivas de estudos, essas moléculas podem ser alvos importantes para a investigação de atividades biológicas, como a avaliação da atividade antitumoral, entre outras.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em QuímicaUFSMBrasilQuímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessPseudo-peptídeosCalcogenonucleosídeosReações de UgiSARS-CoV-2Modelagem molecularPseudo-peptidesChalcogenonucleosidesUgi reactionsMolecular dockingCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICASíntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2Synthesis of pseudo-peptides containing chalcogenonucleosides via UGI reactions as pontential SARS-CoV-2 inhibitorsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisRodrigues, Oscar Endrigo Dorneleshttp://lattes.cnpq.br/6536519955416085Dornelles, LucianoDacol, Ionara IrionMorel, Ademir FariasSouza, Diego deVargas, Josimarhttp://lattes.cnpq.br/3966179889958769Rosa, Raquel Mello da10060000000060060060009fef019-ac43-4d8b-83d3-3565e4686d7b4a6e574e-e65d-4245-ac5a-e1efd444ca8f88ff8616-1678-47c5-b3c5-9a8e5085844fda58e2e8-43a8-40a3-8fb9-544a6f59d5ed52890c7c-4e37-40ac-9c8b-5f6ed5dcc9aa60da2236-e29c-4d57-a253-bc830d7534fc69f5e64e-7d1a-4296-856b-68fe52660de8reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGQUIMICA_2023_ROSA_RAQUEL.pdfTES_PPGQUIMICA_2023_ROSA_RAQUEL.pdfTeseapplication/pdf5664114http://repositorio.ufsm.br/bitstream/1/29622/1/TES_PPGQUIMICA_2023_ROSA_RAQUEL.pdf1616fd91beb4708a54ab33fba1ceaa52MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/29622/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/29622/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD531/296222023-07-04 10:28:51.336oai:repositorio.ufsm.br:1/29622TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEKCkNvbSBhIGFwcmVzZW50YcOnw6NvIGRlc3RhIGxpY2Vuw6dhLCB2b2PDqiAobyBhdXRvciAoZXMpIG91IG8gdGl0dWxhciBkb3MgZGlyZWl0b3MgZGUgYXV0b3IpIGNvbmNlZGUgw6AgVW5pdmVyc2lkYWRlCkZlZGVyYWwgZGUgU2FudGEgTWFyaWEgKFVGU00pIG8gZGlyZWl0byBuw6NvLWV4Y2x1c2l2byBkZSByZXByb2R1emlyLCAgdHJhZHV6aXIgKGNvbmZvcm1lIGRlZmluaWRvIGFiYWl4byksIGUvb3UKZGlzdHJpYnVpciBhIHN1YSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gKGluY2x1aW5kbyBvIHJlc3VtbykgcG9yIHRvZG8gbyBtdW5kbyBubyBmb3JtYXRvIGltcHJlc3NvIGUgZWxldHLDtG5pY28gZQplbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mgw6F1ZGlvIG91IHbDrWRlby4KClZvY8OqIGNvbmNvcmRhIHF1ZSBhIFVGU00gcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250ZcO6ZG8sIHRyYW5zcG9yIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbwpwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIHRhbWLDqW0gY29uY29yZGEgcXVlIGEgVUZTTSBwb2RlIG1hbnRlciBtYWlzIGRlIHVtYSBjw7NwaWEgYSBzdWEgdGVzZSBvdQpkaXNzZXJ0YcOnw6NvIHBhcmEgZmlucyBkZSBzZWd1cmFuw6dhLCBiYWNrLXVwIGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIGRlY2xhcmEgcXVlIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyDDqSBvcmlnaW5hbCBlIHF1ZSB2b2PDqiB0ZW0gbyBwb2RlciBkZSBjb25jZWRlciBvcyBkaXJlaXRvcyBjb250aWRvcwpuZXN0YSBsaWNlbsOnYS4gVm9jw6ogdGFtYsOpbSBkZWNsYXJhIHF1ZSBvIGRlcMOzc2l0byBkYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIG7Do28sIHF1ZSBzZWphIGRlIHNldQpjb25oZWNpbWVudG8sIGluZnJpbmdlIGRpcmVpdG9zIGF1dG9yYWlzIGRlIG5pbmd1w6ltLgoKQ2FzbyBhIHN1YSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gY29udGVuaGEgbWF0ZXJpYWwgcXVlIHZvY8OqIG7Do28gcG9zc3VpIGEgdGl0dWxhcmlkYWRlIGRvcyBkaXJlaXRvcyBhdXRvcmFpcywgdm9jw6oKZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc8OjbyBpcnJlc3RyaXRhIGRvIGRldGVudG9yIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBwYXJhIGNvbmNlZGVyIMOgIFVGU00Kb3MgZGlyZWl0b3MgYXByZXNlbnRhZG9zIG5lc3RhIGxpY2Vuw6dhLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3TDoSBjbGFyYW1lbnRlCmlkZW50aWZpY2FkbyBlIHJlY29uaGVjaWRvIG5vIHRleHRvIG91IG5vIGNvbnRlw7pkbyBkYSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gb3JhIGRlcG9zaXRhZGEuCgpDQVNPIEEgVEVTRSBPVSBESVNTRVJUQcOHw4NPIE9SQSBERVBPU0lUQURBIFRFTkhBIFNJRE8gUkVTVUxUQURPIERFIFVNIFBBVFJPQ8ONTklPIE9VCkFQT0lPIERFIFVNQSBBR8OKTkNJQSBERSBGT01FTlRPIE9VIE9VVFJPIE9SR0FOSVNNTyBRVUUgTsODTyBTRUpBIEEgVUZTTQosIFZPQ8OKIERFQ0xBUkEgUVVFIFJFU1BFSVRPVSBUT0RPUyBFIFFVQUlTUVVFUiBESVJFSVRPUyBERSBSRVZJU8ODTyBDT01PClRBTULDiU0gQVMgREVNQUlTIE9CUklHQcOHw5VFUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKQSBVRlNNIHNlIGNvbXByb21ldGUgYSBpZGVudGlmaWNhciBjbGFyYW1lbnRlIG8gc2V1IG5vbWUgKHMpIG91IG8ocykgbm9tZShzKSBkbyhzKQpkZXRlbnRvcihlcykgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIGRhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbywgZSBuw6NvIGZhcsOhIHF1YWxxdWVyIGFsdGVyYcOnw6NvLCBhbMOpbSBkYXF1ZWxhcwpjb25jZWRpZGFzIHBvciBlc3RhIGxpY2Vuw6dhLgoKBiblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-07-04T13:28:51Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 |
dc.title.alternative.eng.fl_str_mv |
Synthesis of pseudo-peptides containing chalcogenonucleosides via UGI reactions as pontential SARS-CoV-2 inhibitors |
title |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 |
spellingShingle |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 Rosa, Raquel Mello da Pseudo-peptídeos Calcogenonucleosídeos Reações de Ugi SARS-CoV-2 Modelagem molecular Pseudo-peptides Chalcogenonucleosides Ugi reactions Molecular docking CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 |
title_full |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 |
title_fullStr |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 |
title_full_unstemmed |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 |
title_sort |
Síntese de pseudo-peptídeos contendo calcogenonucleosídeos via reações de UGI como potenciais inibidores do SARS-CoV-2 |
author |
Rosa, Raquel Mello da |
author_facet |
Rosa, Raquel Mello da |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rodrigues, Oscar Endrigo Dorneles |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6536519955416085 |
dc.contributor.advisor-co1.fl_str_mv |
Dornelles, Luciano |
dc.contributor.referee1.fl_str_mv |
Dacol, Ionara Irion |
dc.contributor.referee2.fl_str_mv |
Morel, Ademir Farias |
dc.contributor.referee3.fl_str_mv |
Souza, Diego de |
dc.contributor.referee4.fl_str_mv |
Vargas, Josimar |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3966179889958769 |
dc.contributor.author.fl_str_mv |
Rosa, Raquel Mello da |
contributor_str_mv |
Rodrigues, Oscar Endrigo Dorneles Dornelles, Luciano Dacol, Ionara Irion Morel, Ademir Farias Souza, Diego de Vargas, Josimar |
dc.subject.por.fl_str_mv |
Pseudo-peptídeos Calcogenonucleosídeos Reações de Ugi SARS-CoV-2 Modelagem molecular |
topic |
Pseudo-peptídeos Calcogenonucleosídeos Reações de Ugi SARS-CoV-2 Modelagem molecular Pseudo-peptides Chalcogenonucleosides Ugi reactions Molecular docking CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Pseudo-peptides Chalcogenonucleosides Ugi reactions Molecular docking |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
In this work, a reaction protocol was developed for a new class of pseudo-peptides through multicomponent reactions (MCR) of the Ugi’s four component reaction (U-4CR) type, starting from chalcogenonucleosides. The synthetic route was planned to have a single reaction step under mild conditions. The U-4CR reactions provide great structural versatility since the four components presented groups that could be modified: amine, aldehyde, carboxylic acid, and isocyanide. This study emphasized the amine component, in which 5'-arylchalcogenyl-3-amino-thymidines 5a-f were employed. The carboxylic acid component was also explored, two types of isocyanates were studied, and only one aldehyde was used in the reactions. The synthetic route involved a one-pot reaction at room temperature using an ethanolic milieu, and the 9a-q products were obtained with yields ranging from 25 to 77%. The products were characterized by 1H and 13C NMR spectroscopy, and also HRMS. Two-dimensional 1H and 13C NMR experiments were carried out, however, the registered spectra exhibited poor resolution and no signal attribution was performed. In silico molecular docking studies were performed to evaluate the possible interactions between the obtained compounds and the main protease (Mpro) of SARS-CoV-2. The seventeen compounds were evaluated, and nine compounds exhibited favorable interactions at the stable position close to the active site of the Mpro of SARS-CoV-2, with a highlight for compounds 9b and 9h, whose binding energies with Mpro are -8.7 and -8.8 kcal mol-1, respectively, which are bigger than the exhibit by the standard drug nirmatrelvir. In concluding remarks, seventeen new molecules were synthesized in good yields, making clear the success of Ugi 4-CR reactions in forming pseudo-peptides using chalcogenonucleosides. As prospects for further studies, these molecules can be important targets for investigating biological activities, such as evaluating antitumor activity, among others. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-07-04T13:28:51Z |
dc.date.available.fl_str_mv |
2023-07-04T13:28:51Z |
dc.date.issued.fl_str_mv |
2023-03-30 |
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.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/29622 |
url |
http://repositorio.ufsm.br/handle/1/29622 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
100600000000 |
dc.relation.confidence.fl_str_mv |
600 600 600 |
dc.relation.authority.fl_str_mv |
09fef019-ac43-4d8b-83d3-3565e4686d7b 4a6e574e-e65d-4245-ac5a-e1efd444ca8f 88ff8616-1678-47c5-b3c5-9a8e5085844f da58e2e8-43a8-40a3-8fb9-544a6f59d5ed 52890c7c-4e37-40ac-9c8b-5f6ed5dcc9aa 60da2236-e29c-4d57-a253-bc830d7534fc 69f5e64e-7d1a-4296-856b-68fe52660de8 |
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.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Química |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Química |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do 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 |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/29622/1/TES_PPGQUIMICA_2023_ROSA_RAQUEL.pdf http://repositorio.ufsm.br/bitstream/1/29622/2/license_rdf http://repositorio.ufsm.br/bitstream/1/29622/3/license.txt |
bitstream.checksum.fl_str_mv |
1616fd91beb4708a54ab33fba1ceaa52 4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1793240131818225664 |