Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/30830 |
Resumo: | The search for synthetic strategies that allow the efficient hybridization of biologically active molecules has gained attention among researchers, since they allow access to wide multiactive pharmacological varieties. In this sense, a series of molecules were synthesized in this work using 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride), due to its properties that allow its functionalization with a versatility of molecules in a regiochemical way. Unpublished compounds derived from cyanuric chloride were obtained and characterized with different 5'arylcalcogenyl-3-amino-thymidine derivatives of zidovudine. Based on in silico tests, compounds 5a-5i showed favorable molecular docking results for interaction with the main protease active site of SARS-CoV-2, indicating promising antiviral activity. In silico and in vitro assays of the compounds obtained were also carried out to evaluate the antitumor activity. The in silico studies were carried out for the αβ-tubulin protein (dimer) and the in vitro studies against two cancer cell lines H-29 and NCI/ADR-RES, which showed effective inhibitory activity at low concentrations, highlighting the compound 5b. Studies of antioxidant activity were also performed by TBARS assay in which compound 5b at concentrations of 10 μM, 20 μM C and 200 μM significantly prevented lipid peroxidation induced by 100 μM FeSO4 in phosphatidylcholine samples. |
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2023-12-11T14:21:43Z2023-12-11T14:21:43Z2023-09-29http://repositorio.ufsm.br/handle/1/30830The search for synthetic strategies that allow the efficient hybridization of biologically active molecules has gained attention among researchers, since they allow access to wide multiactive pharmacological varieties. In this sense, a series of molecules were synthesized in this work using 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride), due to its properties that allow its functionalization with a versatility of molecules in a regiochemical way. Unpublished compounds derived from cyanuric chloride were obtained and characterized with different 5'arylcalcogenyl-3-amino-thymidine derivatives of zidovudine. Based on in silico tests, compounds 5a-5i showed favorable molecular docking results for interaction with the main protease active site of SARS-CoV-2, indicating promising antiviral activity. In silico and in vitro assays of the compounds obtained were also carried out to evaluate the antitumor activity. The in silico studies were carried out for the αβ-tubulin protein (dimer) and the in vitro studies against two cancer cell lines H-29 and NCI/ADR-RES, which showed effective inhibitory activity at low concentrations, highlighting the compound 5b. Studies of antioxidant activity were also performed by TBARS assay in which compound 5b at concentrations of 10 μM, 20 μM C and 200 μM significantly prevented lipid peroxidation induced by 100 μM FeSO4 in phosphatidylcholine samples.A busca por estratégias sintéticas que permitem a hibridização de moléculas biologicamente ativas de maneira eficiente tem ganhado atenção entre pesquisadores, uma vez que possibilitam acesso a amplas variedades farmacológicas multiativas. Nesse sentido, foram sintetizadas neste trabalho uma série de moléculas utilizando o 2,4,6-tricloro-1,3,5-triazina (cloreto cianúrico), em virtude de suas propriedades que permitem sua funcionalização com uma versatilidade de moléculas de maneira regioquímica. Foram obtidos e caracterizados compostos inéditos derivados do cloreto cianúrico (1,3,4-triazina-2,4,6-tricloro) com diferentes 5’arilcalcogenil-3-amino-timidina derivados de zidovudina. Com base nos testes in silico os compostos 5a-5i apresentaram resultados de ancoragem molecular favoráveis para a interação com o sítio ativo da protease principal do SARS-CoV-2, indicando atividade antiviral promissora. Foram realizados também ensaios in sílico e ensaios in vitro dos compostos obtidos para avaliar a atividade antitumoral. Os estudos in sílico foram realizados para a proteína αβ-tubulina (dímero) e os in vitro frente a duas linhagens de células cancerígenas H-29 e NCI/ADR-RES, os quais apresentaram atividade inibitória eficaz em baixas concentrações, destacando-se o composto 5b. Foram ainda, realizados estudos da atividade antioxidante por ensaio TBARS no qual o composto 5b em concentrações de 10 μM, 20 μM e 200 μM preveniu significativamente a peroxidação lipídica induzida por 100 μM de FeSO4 em amostras de fosfatidilcolinao.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/openAccessCloreto cianúricoHíbridos molecularesOrganocalcogênioZidovudinaCyanuric chlorideMolecular hybridsOrganochalcogenZidovudineCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICASíntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazinaSynthesis and biological evaluation of new molecular hybrids derived from 5'arylcalcogenil-3-amino-thymidine and 2,4,6-trichloro-1,3,5-triazineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisRodrigues, Oscar Endrigo Dorneleshttp://lattes.cnpq.br/6536519955416085Dorneles, LucianoDalcon, Ionara IrionAraújo, Lidiane da Silvahttp://lattes.cnpq.br/1643452571428336Rocha, Nayra Salazar10060000000060060060060060060009fef019-ac43-4d8b-83d3-3565e4686d7b2758d0e2-552e-4a4d-9f3b-0d4494691ebab1412d7c-28f1-4033-bbc7-7bc808cbf68045caf51b-e8e4-415d-8eda-bd79d12512e275a1ffe8-a8c2-46b2-8408-9269db5fd952reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/30830/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/30830/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53ORIGINALDIS_PPGQUIMICA_2023_ROCHA_NAYRA.pdfDIS_PPGQUIMICA_2023_ROCHA_NAYRA.pdfDissertaçãoapplication/pdf7259696http://repositorio.ufsm.br/bitstream/1/30830/1/DIS_PPGQUIMICA_2023_ROCHA_NAYRA.pdfffae7f3e1c8d48af0ae930f3ae08d6d2MD511/308302023-12-11 11:21:44.033oai:repositorio.ufsm.br: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ório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestouvidoria@ufsm.bropendoar:39132023-12-11T14:21:44Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina |
dc.title.alternative.eng.fl_str_mv |
Synthesis and biological evaluation of new molecular hybrids derived from 5'arylcalcogenil-3-amino-thymidine and 2,4,6-trichloro-1,3,5-triazine |
title |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina |
spellingShingle |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina Rocha, Nayra Salazar Cloreto cianúrico Híbridos moleculares Organocalcogênio Zidovudina Cyanuric chloride Molecular hybrids Organochalcogen Zidovudine CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina |
title_full |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina |
title_fullStr |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina |
title_full_unstemmed |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina |
title_sort |
Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina |
author |
Rocha, Nayra Salazar |
author_facet |
Rocha, Nayra Salazar |
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 |
Dorneles, Luciano |
dc.contributor.referee1.fl_str_mv |
Dalcon, Ionara Irion |
dc.contributor.referee2.fl_str_mv |
Araújo, Lidiane da Silva |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1643452571428336 |
dc.contributor.author.fl_str_mv |
Rocha, Nayra Salazar |
contributor_str_mv |
Rodrigues, Oscar Endrigo Dorneles Dorneles, Luciano Dalcon, Ionara Irion Araújo, Lidiane da Silva |
dc.subject.por.fl_str_mv |
Cloreto cianúrico Híbridos moleculares Organocalcogênio Zidovudina |
topic |
Cloreto cianúrico Híbridos moleculares Organocalcogênio Zidovudina Cyanuric chloride Molecular hybrids Organochalcogen Zidovudine CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Cyanuric chloride Molecular hybrids Organochalcogen Zidovudine |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
The search for synthetic strategies that allow the efficient hybridization of biologically active molecules has gained attention among researchers, since they allow access to wide multiactive pharmacological varieties. In this sense, a series of molecules were synthesized in this work using 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride), due to its properties that allow its functionalization with a versatility of molecules in a regiochemical way. Unpublished compounds derived from cyanuric chloride were obtained and characterized with different 5'arylcalcogenyl-3-amino-thymidine derivatives of zidovudine. Based on in silico tests, compounds 5a-5i showed favorable molecular docking results for interaction with the main protease active site of SARS-CoV-2, indicating promising antiviral activity. In silico and in vitro assays of the compounds obtained were also carried out to evaluate the antitumor activity. The in silico studies were carried out for the αβ-tubulin protein (dimer) and the in vitro studies against two cancer cell lines H-29 and NCI/ADR-RES, which showed effective inhibitory activity at low concentrations, highlighting the compound 5b. Studies of antioxidant activity were also performed by TBARS assay in which compound 5b at concentrations of 10 μM, 20 μM C and 200 μM significantly prevented lipid peroxidation induced by 100 μM FeSO4 in phosphatidylcholine samples. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-12-11T14:21:43Z |
dc.date.available.fl_str_mv |
2023-12-11T14:21:43Z |
dc.date.issued.fl_str_mv |
2023-09-29 |
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/1/30830 |
url |
http://repositorio.ufsm.br/handle/1/30830 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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100600000000 |
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600 600 600 600 600 600 |
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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:Repositório Institucional Manancial UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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