Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/7644 |
Resumo: | This work involves the synthesis and characterization of three new series of ruthenium complexes containing gallic acid and derivatives cinnamic acid and salicylic acid and derivatives, as these ligands exhibit interesting biological properties. All ligands are synthetic and natural products can be found in the daily diet. The interest in studying these three ligands series is due to the antioxidant power that some of these natural products present. Thus, complexes of formula [Ru(O-O)(dppb)(bipy)]PF6 and [Ru(O-O)(dppe)2]PF6 , where O-O = gallic acid and derivatives, cinnamic acid and salicylic acid and derivatives (bipy = 2,2'-bipyridine, dppb = 1,4-bis(diphenylphosphino)butane and dppe = 1,2- bis(diphenylphosphino)ethane). All the synthesized compounds were characterized by molar conductivity, elemental analysis, absorption spectra in the infrared, absorption spectroscopy in the UV-visible region, mass spectrometry, nuclear magnetic resonance 31P {1H}, cyclic voltammetry and differential pulse, and for some complexes, X-ray crystallography. The evaluation of the biological potential of ruthenium complexes with different series of ligands were evaluated: the partition coefficient, the antioxidant activity, morphological study, clonogenic assay in MDA-MB-231 and L929, cytotoxic activity in tumor cell lines MDA MB-231, MCF-7 and A549, and nontumor cell lines of mouse and hamster V79 and L929, respectively. Cell viability assays show promising results, indicating a greater cytotoxicity of the complexes in MDA-MB-231 line with respect to the other tumor cell line. Furthermore, the complexes of general formula [Ru(O-O)(dppe)2]PF6 exhibit the values lowest of IC50 in compared on the complexes of the general formula [Ru(O-O)(dppb)(bipy)]PF6 in all the cell line studied. Studies of the interaction of the complexes with bovine serum albumin (BSA), were performed, and compounds have moderate to strong interaction with the protein, and the complexes containing two dppe biphosphinas have smaller constant values in relation the complexes of the series [Ru(O-O)(dppb)(bipy)]PF6. |
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Graminha, Angelica EllenBatista, Alzir Azevedohttp://lattes.cnpq.br/6469642481998660http://lattes.cnpq.br/5346291554255235b4e5db98-7876-4f84-91dc-4b451ff0972a2016-10-04T18:17:01Z2016-10-04T18:17:01Z2015-02-26GRAMINHA, Angelica Ellen. Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica. 2015. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2015. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7644.https://repositorio.ufscar.br/handle/ufscar/7644This work involves the synthesis and characterization of three new series of ruthenium complexes containing gallic acid and derivatives cinnamic acid and salicylic acid and derivatives, as these ligands exhibit interesting biological properties. All ligands are synthetic and natural products can be found in the daily diet. The interest in studying these three ligands series is due to the antioxidant power that some of these natural products present. Thus, complexes of formula [Ru(O-O)(dppb)(bipy)]PF6 and [Ru(O-O)(dppe)2]PF6 , where O-O = gallic acid and derivatives, cinnamic acid and salicylic acid and derivatives (bipy = 2,2'-bipyridine, dppb = 1,4-bis(diphenylphosphino)butane and dppe = 1,2- bis(diphenylphosphino)ethane). All the synthesized compounds were characterized by molar conductivity, elemental analysis, absorption spectra in the infrared, absorption spectroscopy in the UV-visible region, mass spectrometry, nuclear magnetic resonance 31P {1H}, cyclic voltammetry and differential pulse, and for some complexes, X-ray crystallography. The evaluation of the biological potential of ruthenium complexes with different series of ligands were evaluated: the partition coefficient, the antioxidant activity, morphological study, clonogenic assay in MDA-MB-231 and L929, cytotoxic activity in tumor cell lines MDA MB-231, MCF-7 and A549, and nontumor cell lines of mouse and hamster V79 and L929, respectively. Cell viability assays show promising results, indicating a greater cytotoxicity of the complexes in MDA-MB-231 line with respect to the other tumor cell line. Furthermore, the complexes of general formula [Ru(O-O)(dppe)2]PF6 exhibit the values lowest of IC50 in compared on the complexes of the general formula [Ru(O-O)(dppb)(bipy)]PF6 in all the cell line studied. Studies of the interaction of the complexes with bovine serum albumin (BSA), were performed, and compounds have moderate to strong interaction with the protein, and the complexes containing two dppe biphosphinas have smaller constant values in relation the complexes of the series [Ru(O-O)(dppb)(bipy)]PF6.Este trabalho envolve a síntese e caracterização de três novas séries de complexos de rutênio contendo ácido gálico e derivados, ácidos cinâmicos e ácido salicílico e derivados, uma vez que estes ligantes apresentam propriedades biológicas interessantes. Todos os ligantes são produtos naturais sintéticos e podem ser encontrados diariamente na dieta alimentar. O interesse em estudar estas três séries de ligantes é devido ao poder antioxidante que alguns destes produtos naturais apresentam. Assim, complexos de fórmula geral [Ru(OO)(dppb)(bipy)]PF6 e [Ru(O-O)(dppe)2]PF6 onde O-O = ácido gálico e derivados, ácidos cinâmicos e ácido salicílico e derivados (bipy = 2,2’-bipiridina, dppb = 1,4-bis(difenilfosfina)butano e dppe = 1,2-bis(difenilfosfina)etano). Todos os complexos sintetizados foram caracterizados por condutividade molar, análise elementar, espectroscopia de absorção na região do infravermelho, espectroscopia de absorção na região do UV-visível, espectrometria de massa, ressonância magnética nuclear de 31P{1H}, voltametria cíclica e de pulso diferencial, e para alguns complexos, raios X de monocristal. A avaliação do potencial biológico dos complexos de rutênio com as diferentes séries dos ligantes foram avaliados: o coeficiente de partição, a atividade antioxidante, estudo morfológico, ensaio clonogênico nas linhagens MDA-MB-231 e L929, a atividade citotóxica nas linhagens tumorais MDA-MB-231, MCF-7 e A549, e nas linhagens não-tumorais de camundongo e hamster L929 e V79, respectivamente. Os ensaios de viabilidade celular apresentam resultados promissores, indicando uma maior citotoxidade dos complexos na linhagem MDA-MB-231 em relação às outras linhagens tumorais. Além disso, os complexos sintetizados com fórmula geral [Ru(O-O)(dppe)2]PF6, apresentam os menores valores de IC50 em relação aos complexos de fórmula geral [Ru(OO)(dppb)(bipy)]PF6, em todas as linhagens celular estudadas. Os estudos da interação dos complexos, com a albumina sérica bovina (BSA), foram realizados, e os compostos apresentam interação de moderada a forte com a proteína, sendo que os complexos contendo duas bifosfinas dppe apresentam valores de constante menores em relação a serie de complexos derivados [Ru(OO)(dppb)(bipy)]PF6.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarComplexos de rutênioCâncerProdutos naturaisAtividade citotóxicasInteração com BSACIENCIAS EXATAS E DA TERRA::QUIMICACIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICAProdutos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxicaNatural products and derivatives, complexation with ruthenium targeting increased cytotoxicity activityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOnline600600e62fb48f-fa23-4158-8d60-0b17f006946cinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTeseAEG.pdfTeseAEG.pdfapplication/pdf15370614https://repositorio.ufscar.br/bitstream/ufscar/7644/1/TeseAEG.pdfc13dee6bd3fd353a20f2d379afae1994MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/7644/2/license.txtae0398b6f8b235e40ad82cba6c50031dMD52TEXTTeseAEG.pdf.txtTeseAEG.pdf.txtExtracted texttext/plain290381https://repositorio.ufscar.br/bitstream/ufscar/7644/3/TeseAEG.pdf.txtd848b7cbfe88a9988bffed0a1547406dMD53THUMBNAILTeseAEG.pdf.jpgTeseAEG.pdf.jpgIM Thumbnailimage/jpeg8312https://repositorio.ufscar.br/bitstream/ufscar/7644/4/TeseAEG.pdf.jpg48a8f7a7306bbfcac296dd32599453dcMD54ufscar/76442023-09-18 18:30:52.828oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:30:52Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica |
dc.title.alternative.eng.fl_str_mv |
Natural products and derivatives, complexation with ruthenium targeting increased cytotoxicity activity |
title |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica |
spellingShingle |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica Graminha, Angelica Ellen Complexos de rutênio Câncer Produtos naturais Atividade citotóxicas Interação com BSA CIENCIAS EXATAS E DA TERRA::QUIMICA CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICA |
title_short |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica |
title_full |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica |
title_fullStr |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica |
title_full_unstemmed |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica |
title_sort |
Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica |
author |
Graminha, Angelica Ellen |
author_facet |
Graminha, Angelica Ellen |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/5346291554255235 |
dc.contributor.author.fl_str_mv |
Graminha, Angelica Ellen |
dc.contributor.advisor1.fl_str_mv |
Batista, Alzir Azevedo |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6469642481998660 |
dc.contributor.authorID.fl_str_mv |
b4e5db98-7876-4f84-91dc-4b451ff0972a |
contributor_str_mv |
Batista, Alzir Azevedo |
dc.subject.por.fl_str_mv |
Complexos de rutênio Câncer Produtos naturais Atividade citotóxicas Interação com BSA |
topic |
Complexos de rutênio Câncer Produtos naturais Atividade citotóxicas Interação com BSA CIENCIAS EXATAS E DA TERRA::QUIMICA CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICA |
description |
This work involves the synthesis and characterization of three new series of ruthenium complexes containing gallic acid and derivatives cinnamic acid and salicylic acid and derivatives, as these ligands exhibit interesting biological properties. All ligands are synthetic and natural products can be found in the daily diet. The interest in studying these three ligands series is due to the antioxidant power that some of these natural products present. Thus, complexes of formula [Ru(O-O)(dppb)(bipy)]PF6 and [Ru(O-O)(dppe)2]PF6 , where O-O = gallic acid and derivatives, cinnamic acid and salicylic acid and derivatives (bipy = 2,2'-bipyridine, dppb = 1,4-bis(diphenylphosphino)butane and dppe = 1,2- bis(diphenylphosphino)ethane). All the synthesized compounds were characterized by molar conductivity, elemental analysis, absorption spectra in the infrared, absorption spectroscopy in the UV-visible region, mass spectrometry, nuclear magnetic resonance 31P {1H}, cyclic voltammetry and differential pulse, and for some complexes, X-ray crystallography. The evaluation of the biological potential of ruthenium complexes with different series of ligands were evaluated: the partition coefficient, the antioxidant activity, morphological study, clonogenic assay in MDA-MB-231 and L929, cytotoxic activity in tumor cell lines MDA MB-231, MCF-7 and A549, and nontumor cell lines of mouse and hamster V79 and L929, respectively. Cell viability assays show promising results, indicating a greater cytotoxicity of the complexes in MDA-MB-231 line with respect to the other tumor cell line. Furthermore, the complexes of general formula [Ru(O-O)(dppe)2]PF6 exhibit the values lowest of IC50 in compared on the complexes of the general formula [Ru(O-O)(dppb)(bipy)]PF6 in all the cell line studied. Studies of the interaction of the complexes with bovine serum albumin (BSA), were performed, and compounds have moderate to strong interaction with the protein, and the complexes containing two dppe biphosphinas have smaller constant values in relation the complexes of the series [Ru(O-O)(dppb)(bipy)]PF6. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-02-26 |
dc.date.accessioned.fl_str_mv |
2016-10-04T18:17:01Z |
dc.date.available.fl_str_mv |
2016-10-04T18:17:01Z |
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 |
GRAMINHA, Angelica Ellen. Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica. 2015. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2015. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7644. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/7644 |
identifier_str_mv |
GRAMINHA, Angelica Ellen. Produtos naturais e derivados, complexação com o rutênio visando aumento da atividade citotóxica. 2015. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2015. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7644. |
url |
https://repositorio.ufscar.br/handle/ufscar/7644 |
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por |
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por |
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600 600 |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de São Carlos Câmpus São Carlos |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Química - PPGQ |
dc.publisher.initials.fl_str_mv |
UFSCar |
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Universidade Federal de São Carlos Câmpus São Carlos |
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