Síntese, caracterização e avaliação da atividade antitumoral de Complexos de Ru(II) à base de ligantes fenâmicos.

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dc.contributor.advisorCorrea, Rodrigo de Souzapt_BR
dc.contributor.advisorOliveira, Katia Mara dept_BR
dc.contributor.authorCarvalho, Diogo Emerson Leite de
dc.contributor.refereeCorrea, Rodrigo de Souzapt_BR
dc.contributor.refereeCaldeira, Priscila Pereira Silvapt_BR
dc.contributor.refereeSilveira, Rafael Gomes dapt_BR
dc.date.accessioned2023-03-07T21:01:10Z
dc.date.available2023-03-07T21:01:10Z
dc.date.issued2021pt_BR
dc.descriptionPrograma de Pós-Graduação em Química. Departamento de Química, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto.pt_BR
dc.description.abstractO presente trabalho envolve a obtenção, caracterização e avaliação da atividade citotóxica frente à células tumorais de quatro novos complexos de rutênio(II) contendo ligantes de interesse biológico, pertencentes à classe de anti-inflamatórios não esteroidais. Para a síntese dos novos compostos utilizou-se o complexo precursor trans-[RuCl2(dppe)2], onde dppe = 1,2- bis(difenilfosfina)etano e como ligantes (L) os ácidos fenâmico (fe), tolfenâmico (tol), mefenâmico (me) e flufenâmico (flu), para formar complexos de fórmula geral [Ru(L)(dppe)2]PF6. Os compostos obtidos foram caracterizados por diversas técnicas, tais como espectroscopia de ressonância magnética nuclear de 31P{1H}, 1H, 13C{1H}, voltametria cíclica, condutimetria, análise elementar, espectroscopia de absorção na região do ultravioleta/visível, espectroscopia de absorção na região do infravermelho e difração de raios X por monocristal. A atividade citotóxica dos complexos obtidos foi avaliada frente as linhagens de células tumorais de mama (MDA-MB-231) e pulmão (A549) e não tumoral de pulmão (MRC-5). Todos os complexos demonstraram significativa citotoxicidade frente as linhagens celulares investigadas, com valores de IC50 na faixa de 0,94 – 17,71 μM. Além disso, com exceção do complexo com ácido tolfenâmico, o [Ru(tol)(dppe)2]PF6, todos os demais complexos foram mais citotóxicos do que a cisplatina, fármaco utilizado como referência. O complexo [Ru(me)(dppe)2]PF6 que apresentou alto índice de seletividade frente a linhagem A549. No caso da linhagem MDA-MB-231, o complexo mais seletivo foi o [Ru(fe)(dppe)2]PF6, com bom índice de seletividade. Os complexos foram avaliados quanto a interação com a Albumina de Soro Bovino (BSA) e os resultados demonstraram uma interação moderada com essa proteína, por meio dos mecanismos dinâmico e estático. As interações complexo-BSA são de natureza hidrofóbicas, com exceção do complexo [Ru(fe)(dppe)2]PF6, que predomina as interações eletrostáticas. Estudos de interação com o CT-DNA (Calf-Thymus DNA) por meio de titulações espectroscópicas e medidas de viscosidade demonstraram que os complexos interagem fracamente com o DNA, sendo muito provavelmente por interações eletrostáticas, tendo em vista que os complexos apresentam carga positiva e a molécula de DNA possui carga negativa devido a presença dos grupos fosfato.pt_BR
dc.description.abstractenThe present report is dedicated to the synthesis, characterization, and cytotoxic activity against tumor cells of four new ruthenium(II) complexes containing ligands of biological interest (fenamic), belonging to the class of non-steroidal anti-inflammatory drugs. For the synthesis of the new compounds, the trans-[RuCl2(dppe)2] precursor complex, where dppe = 1,2- bis(diphenylphosphine)ethane, and the fenamic (fe), mefenamic (me), tolfenamic (tol) and flufenamic (flu) acids were used. The compounds were characterized by several techniques, such as 31P{1H}, 1H, 13C{1H} nuclear magnetic resonance spectroscopy, cyclic voltammetry, conductometry, elemental analysis, ultraviolet/visible, infrared absorption spectroscopy, and single-crystal X-ray diffraction for all complexes. The cytotoxic activity of the complexes was evaluated against the breast tumor cell lines (MDA-MB-231) and lung (A549), as well as non- tumor lung ones (MRC-5). All complexes showed significant cytotoxicity against tumor cell lines, with IC50 values in the range from 0.94 to 17.71 μM. Except the [Ru(tol)(dppe)2]PF6 complex, all complexes were more cytotoxic than cisplatin, a drug used as a reference. The [Ru(me)(dppe)2]PF6 complex presents a selectivity index against the A549 line. Regarding the cytotoxic against MDA-MB-231 cells, [Ru(fe)(dppe)2]PF6 was the most selective complex with a good selectivity. Finally, complexes/BSA (Bovine Serum Albumin) interaction studies reveal moderate forces occurring between them, involving dynamic and static mechanisms. Probably, the nature of complex/BSA interactions occurs by hydrophobic forces, except to the [Ru(fe)(dppe)2]PF6 complex, which predominates electrostatic interactions. Complex/CT-DNA (Calf-Thymus DNA) interactions by spectroscopic titrations and viscosity measurements show that complexes interact weakly with DNA. This interaction can be due to electrostatic attraction, given that all complexes are cationic and can be attracted by the negative charge of phosphate groups of DNA.The present report is dedicated to the synthesis, characterization, and cytotoxic activity against tumor cells of four new ruthenium(II) complexes containing ligands of biological interest (fenamic), belonging to the class of non-steroidal anti-inflammatory drugs. For the synthesis of the new compounds, the trans-[RuCl2(dppe)2] precursor complex, where dppe = 1,2- bis(diphenylphosphine)ethane, and the fenamic (fe), mefenamic (me), tolfenamic (tol) and flufenamic (flu) acids were used. The compounds were characterized by several techniques, such as 31P{1H}, 1H, 13C{1H} nuclear magnetic resonance spectroscopy, cyclic voltammetry, conductometry, elemental analysis, ultraviolet/visible, infrared absorption spectroscopy, and single-crystal X-ray diffraction for all complexes. The cytotoxic activity of the complexes was evaluated against the breast tumor cell lines (MDA-MB-231) and lung (A549), as well as non- tumor lung ones (MRC-5). All complexes showed significant cytotoxicity against tumor cell lines, with IC50 values in the range from 0.94 to 17.71 μM. Except the [Ru(tol)(dppe)2]PF6 complex, all complexes were more cytotoxic than cisplatin, a drug used as a reference. The [Ru(me)(dppe)2]PF6 complex presents a selectivity index against the A549 line. Regarding the cytotoxic against MDA-MB-231 cells, [Ru(fe)(dppe)2]PF6 was the most selective complex with a good selectivity. Finally, complexes/BSA (Bovine Serum Albumin) interaction studies reveal moderate forces occurring between them, involving dynamic and static mechanisms. Probably, the nature of complex/BSA interactions occurs by hydrophobic forces, except to the [Ru(fe)(dppe)2]PF6 complex, which predominates electrostatic interactions. Complex/CT-DNA (Calf-Thymus DNA) interactions by spectroscopic titrations and viscosity measurements show that complexes interact weakly with DNA. This interaction can be due to electrostatic attraction, given that all complexes are cationic and can be attracted by the negative charge of phosphate groups of DNA.The present report is dedicated to the synthesis, characterization, and cytotoxic activity against tumor cells of four new ruthenium(II) complexes containing ligands of biological interest (fenamic), belonging to the class of non-steroidal anti-inflammatory drugs. For the synthesis of the new compounds, the trans-[RuCl2(dppe)2] precursor complex, where dppe = 1,2- bis(diphenylphosphine)ethane, and the fenamic (fe), mefenamic (me), tolfenamic (tol) and flufenamic (flu) acids were used. The compounds were characterized by several techniques, such as 31P{1H}, 1H, 13C{1H} nuclear magnetic resonance spectroscopy, cyclic voltammetry, conductometry, elemental analysis, ultraviolet/visible, infrared absorption spectroscopy, and single-crystal X-ray diffraction for all complexes. The cytotoxic activity of the complexes was evaluated against the breast tumor cell lines (MDA-MB-231) and lung (A549), as well as non- tumor lung ones (MRC-5). All complexes showed significant cytotoxicity against tumor cell lines, with IC50 values in the range from 0.94 to 17.71 μM. Except the [Ru(tol)(dppe)2]PF6 complex, all complexes were more cytotoxic than cisplatin, a drug used as a reference. The [Ru(me)(dppe)2]PF6 complex presents a selectivity index against the A549 line. Regarding the cytotoxic against MDA-MB-231 cells, [Ru(fe)(dppe)2]PF6 was the most selective complex with a good selectivity. Finally, complexes/BSA (Bovine Serum Albumin) interaction studies reveal moderate forces occurring between them, involving dynamic and static mechanisms. Probably, the nature of complex/BSA interactions occurs by hydrophobic forces, except to the [Ru(fe)(dppe)2]PF6 complex, which predominates electrostatic interactions. Complex/CT-DNA (Calf-Thymus DNA) interactions by spectroscopic titrations and viscosity measurements show that complexes interact weakly with DNA. This interaction can be due to electrostatic attraction, given that all complexes are cationic and can be attracted by the negative charge of phosphate groups of DNA.pt_BR
dc.identifier.citationCARVALHO, Diogo Emerson Leite de. Síntese, caracterização e avaliação da atividade antitumoral de Complexos de Ru(II) à base de ligantes fenâmicos. 2021. 101 f. Dissertação (Mestrado em Química) - Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, 2021.pt_BR
dc.identifier.urihttp://www.repositorio.ufop.br/jspui/handle/123456789/16310
dc.language.isopt_BRpt_BR
dc.rightsabertopt_BR
dc.rights.licenseAutorização concedida ao Repositório Institucional da UFOP pelo(a) autor(a) em 03/01/2022 com as seguintes condições: disponível sob Licença Creative Commons 4.0 que permite copiar, distribuir e transmitir o trabalho, desde que sejam citados o autor e o licenciante.pt_BR
dc.rights.urihttp://creativecommons.org/licenses/by-sa/3.0/us/*
dc.subjectComplexos de rutêniopt_BR
dc.subjectDerivados fenâmicospt_BR
dc.subjectQuimica bioinorgânicapt_BR
dc.subjectMetalofármacospt_BR
dc.titleSíntese, caracterização e avaliação da atividade antitumoral de Complexos de Ru(II) à base de ligantes fenâmicos.pt_BR
dc.typeDissertacaopt_BR
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