Síntese e avaliação biológica de novos híbridos moleculares derivados de 5’-arilcalcogenil-3-amino-timidina e 2,4,6-tricloro- 1,3,5-triazina

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Rocha, Nayra Salazar lattes
Orientador(a): Rodrigues, Oscar Endrigo Dorneles lattes
Banca de defesa: Dalcon, Ionara Irion, Araújo, Lidiane da Silva
Tipo de documento: Dissertação
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:
Cloreto cianúrico
Híbridos moleculares
Organocalcogênio
Zidovudina
Palavras-chave em Inglês:
Cyanuric chloride
Molecular hybrids
Organochalcogen
Zidovudine
Área do conhecimento CNPq:
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
Link de acesso: 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 Unpublished compounds derived from cyanuric chloride were obtained and characterized with different 5'arylcalcogenyl-3-amino-thymidine derivatives of zidovudine.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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spelling 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:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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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
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url http://repositorio.ufsm.br/handle/1/30830
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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
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