Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/14319 |
Resumo: | In this thesis, two series of new Ru-phosphine complexes containing mercapto or acylthiourea ligands were synthesized, characterized and assessed their cytotoxic activities. The first series is composed of five complexes of general formula [Ru(NS)(dphppy)(dppb)]PF6 (AMP1-AMP5) [dpphpy = diphenyl-2-pyridylphosphine, NS = 2-mercaptopyridine (pyS; AMP1), 2-thiazoline-2-thiol (tzdt; AMP2), 6-mercaptopyridine-3-carboxylic acid (mpca, AMP3), 2-mercaptopyrimidine (pySm, AMP4) and 4,6-diamino-2-mercaptopyrimidine (damp, AMP5); dppb = 1,4-bis(diphenylphosphino)butane]. In the second series, complexes present the general formula [Ru(OS)(dphppy)(dppb)]PF6 (SPPM2-SPPM6) [OS= N,N-(dimethyl)-N'-benzoylthiourea (dmbth; SPPM2), N, N-(diethyl)-N'-benzoylthiourea (debth, SPPM3), N,N-(dipropyl)-N'-benzoylthiourea (SPPM4), N,N-(dibutyl)-N'-benzoylthiourea (dbbth, SPPM5), N,N-(diphenyl)-N'-benzoylthiourea (dpbth, SPPM6)]. The complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV/Visible, 1D and 2D NMR) and X-ray diffraction. In the characterization, the correlation between the phosphorous atoms with their respective aromatic hydrogens of the compounds in the assignment stands out, by 1H-31P HMBC experiments. The cytotoxic activity of the complexes was evaluated against cell lines derived from human tumors, MDA-MB-231 (breast cancer) and A549 (lung cancer) and against non-tumoral human cell lines derived from lung MCR-5 and breast MCF-10A. The compounds showed good to excellent anticancer activities against cancer cell lines, with IC50 values significantly lower than the free ligands and cisplatin. For A549 tumor cells, the complexes with mercaptos had IC50 values in the range of 0.12-2.59 µM, and the complexes with acylthiourea in the range of 0.10-0.98 µM. In the breast tumor cells, IC50 values were in the range of 0.08-0.36 µM and 0.25-1.05 µM for the AMP and SPPM series, respectively. All complexes were also selective for tumor cells in comparison to the respective non-tumoral cell lines. The complexes with acylthiourea showed expressive selectivity toward lung tumor cells, with selectivity indexes (SI) values above (or equal to) 10. The compounds AMP4 (SI= 6.7) and SPPM4 (SI= 33) were chosen for further studies in lung tumor cells, due to the better selectivity index in their respective series. Both complexes were able to inhibit colony formation and alter the morphology of tumor cells A549. In the cell cycle analysis of the cells, the complexes induced an accumulation of cells with abnormal content, called Sub-G1 cells, which represents the fraction of dead cells and fragmented DNA. The fragmentation of DNA is due to the cell apoptosis process, confirmed for cells treated with the AMP4. For A549 cells treated with the SPPM4 complex, possibly other cell death processes are involved. The possible biological targets of the complexes that could act as triggers for the cell death process were also studied. The complexes presented weak reversible interactions via minor groove of the DNA. The complexes caused no significant changes in the tertiary and secondary DNA structures, indicating that this biomolecule is probably not the primary target for them. Study with enzymatic target, especially targets overexpressed in tumor cells that justify the cytotoxic activity of the compounds were carried out. And it was found that the complexes are capable of partially inhibiting the Top IB catalytic activity, at low concentrations, close to the IC50 values of cancer cell lines. Overall, the proteasome enzyme can be a biological target for these complexes. The results indicate that ruthenium complexes containing mercaptos or acylthiourea present promising cytotoxic activities for the development of chemotherapeutics for the treatment of cancer. Among the complexes assayed in HEK293T-uGFP cells, complex AMP5 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent, indicating that the proteasome 26S enzyme can be a biological target of the compound. |
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Ribeiro, Gabriel HenriqueBatista, Alzir Azevedohttp://lattes.cnpq.br/6469642481998660http://lattes.cnpq.br/37016167955985112021-05-27T11:30:55Z2021-05-27T11:30:55Z2020-12-11RIBEIRO, Gabriel Henrique. Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias. 2020. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2020. Disponível em: https://repositorio.ufscar.br/handle/ufscar/14319.https://repositorio.ufscar.br/handle/ufscar/14319In this thesis, two series of new Ru-phosphine complexes containing mercapto or acylthiourea ligands were synthesized, characterized and assessed their cytotoxic activities. The first series is composed of five complexes of general formula [Ru(NS)(dphppy)(dppb)]PF6 (AMP1-AMP5) [dpphpy = diphenyl-2-pyridylphosphine, NS = 2-mercaptopyridine (pyS; AMP1), 2-thiazoline-2-thiol (tzdt; AMP2), 6-mercaptopyridine-3-carboxylic acid (mpca, AMP3), 2-mercaptopyrimidine (pySm, AMP4) and 4,6-diamino-2-mercaptopyrimidine (damp, AMP5); dppb = 1,4-bis(diphenylphosphino)butane]. In the second series, complexes present the general formula [Ru(OS)(dphppy)(dppb)]PF6 (SPPM2-SPPM6) [OS= N,N-(dimethyl)-N'-benzoylthiourea (dmbth; SPPM2), N, N-(diethyl)-N'-benzoylthiourea (debth, SPPM3), N,N-(dipropyl)-N'-benzoylthiourea (SPPM4), N,N-(dibutyl)-N'-benzoylthiourea (dbbth, SPPM5), N,N-(diphenyl)-N'-benzoylthiourea (dpbth, SPPM6)]. The complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV/Visible, 1D and 2D NMR) and X-ray diffraction. In the characterization, the correlation between the phosphorous atoms with their respective aromatic hydrogens of the compounds in the assignment stands out, by 1H-31P HMBC experiments. The cytotoxic activity of the complexes was evaluated against cell lines derived from human tumors, MDA-MB-231 (breast cancer) and A549 (lung cancer) and against non-tumoral human cell lines derived from lung MCR-5 and breast MCF-10A. The compounds showed good to excellent anticancer activities against cancer cell lines, with IC50 values significantly lower than the free ligands and cisplatin. For A549 tumor cells, the complexes with mercaptos had IC50 values in the range of 0.12-2.59 µM, and the complexes with acylthiourea in the range of 0.10-0.98 µM. In the breast tumor cells, IC50 values were in the range of 0.08-0.36 µM and 0.25-1.05 µM for the AMP and SPPM series, respectively. All complexes were also selective for tumor cells in comparison to the respective non-tumoral cell lines. The complexes with acylthiourea showed expressive selectivity toward lung tumor cells, with selectivity indexes (SI) values above (or equal to) 10. The compounds AMP4 (SI= 6.7) and SPPM4 (SI= 33) were chosen for further studies in lung tumor cells, due to the better selectivity index in their respective series. Both complexes were able to inhibit colony formation and alter the morphology of tumor cells A549. In the cell cycle analysis of the cells, the complexes induced an accumulation of cells with abnormal content, called Sub-G1 cells, which represents the fraction of dead cells and fragmented DNA. The fragmentation of DNA is due to the cell apoptosis process, confirmed for cells treated with the AMP4. For A549 cells treated with the SPPM4 complex, possibly other cell death processes are involved. The possible biological targets of the complexes that could act as triggers for the cell death process were also studied. The complexes presented weak reversible interactions via minor groove of the DNA. The complexes caused no significant changes in the tertiary and secondary DNA structures, indicating that this biomolecule is probably not the primary target for them. Study with enzymatic target, especially targets overexpressed in tumor cells that justify the cytotoxic activity of the compounds were carried out. And it was found that the complexes are capable of partially inhibiting the Top IB catalytic activity, at low concentrations, close to the IC50 values of cancer cell lines. Overall, the proteasome enzyme can be a biological target for these complexes. The results indicate that ruthenium complexes containing mercaptos or acylthiourea present promising cytotoxic activities for the development of chemotherapeutics for the treatment of cancer. Among the complexes assayed in HEK293T-uGFP cells, complex AMP5 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent, indicating that the proteasome 26S enzyme can be a biological target of the compound.O presente trabalho teve como objetivos principais a síntese, caracterização e avaliação biológica de duas séries de complexos fosfínicos de rutênio contendo ligantes mercaptos ou aciltioureias. A primeira série foi composta de cinco complexos com fórmula geral [Ru(NS)(dphppy)(dppb)]PF6 (AMP1-AMP5) [dppb= 1,4-bis(difenilfosfina)butano; dphppy= 2-(difenilfosfina)piridina; NS= 2-mercaptopiridina (pyS; AMP1), 2-mercaptotiazolina (tzdt; AMP2), 6-mercaptopiridina-3-ácido carboxílico (mpca; AMP3), 2-mercaptopirimidina (pySm; AMP4) e 4,6-diamino-2-mercaptopirimidina (damp; AMP5)]. Os complexos da segunda série apresentaram fórmula geral [Ru(OS)(dphppy)(dppb)]PF6 (SPPM2-SPPM6) [OS (aciltioureias)= dmbth= N,N-(dimetil)-N’-benzoiltioureia (SPPM2), debth= N,N-(dietil)-N’-benzoiltioureia (SPPM3), depth= N,N-(dipropil)-N’-benzoiltioureia (SPPM4), dbbth= N,N-(dibutil)-N’-benzoiltioureia (SPPM5), dfbth= N,N-(difenil)-N’-benzoiltioureia (SPPM6)]. Todos os complexos foram caracterizados pelas técnicas de espectroscopia de absorção na região do infravermelho e do UV/visível, análise elementar, condutividade molar, voltametria cíclica, espectroscopia de ressonância magnética nuclear de 1H, 13C {1H} e 31P {1H} e difração de raios X de monocristais. A atividade citotóxica dos complexos foi avaliada frente às linhagens celulares derivadas de tumores humanos, MDA-MB-231 (câncer de mama) e A549 (câncer de pulmão) e frente às linhagens celulares humanas não tumorais derivadas de pulmão MCR-5 e de mama MCF-10A. Os complexos apresentaram excelentes atividades citotóxicas nas linhagens tumorais, com valores de IC50 significativamente inferiores em relação aos ligantes livres e a cisplatina. Nas células tumorais de pulmão, os complexos com mercaptos apresentaram valores de IC50 na faixa de 0,12-2,59 µM, e os complexos com aciltioureias na faixa de 0,10-0,98 µM. Os valores de IC50 frente às células tumorais de mama foram na faixa de 0,08-0,36 µM e 0,25-1,05 µM para as séries AMP e SPPM, respectivamente. Os complexos também apresentaram seletividade pelas células tumorais MDA-MB-231 e A549 em relação às respectivas linhagens celulares não tumorais. Destaca-se a seletividade dos complexos com ligantes aciltioureias pela linhagem A549, com índices de seletividade acima ou igual a 10. Os compostos AMP4 (IS= 6,7) e SPPM4 (IS= 33) foram escolhidos para estudos adicionais nas células tumorais de pulmão, devido aos melhores índices de seletividade em sua respectiva série. Ambos os complexos foram capazes de inibir a formação de colônias e alterar a morfologia das células tumorais da linhagem A549. Na análise do ciclo celular, os complexos induziram um acúmulo de células com conteúdo anormal de DNA, denominadas de células Sub-G1, que representa a fração de células mortas e com DNA fragmentado. A fragmentação do DNA pode ser referente ao processo de apoptose celular, confirmado para as células tratadas com o AMP4. Para as células A549 tratadas com o complexo SPPM4, possivelmente outros processos de morte celular estão envolvidos. Também foram estudados possíveis alvos biológicos dos complexos que possam atuar como gatilhos para desencadear o processo de morte celular. Os complexos apresentaram interações reversíveis e fracas via sulco menor do DNA, porém não causam alterações nas estruturas secundaria e terciaria da biomolécula. Tais resultados apontam que provavelmente o DNA não é o alvo principal dos compostos. A inibição da atividade da enzima topoisomerase IB pelos complexos com os ligantes mercaptos foi analisada pelo processo de relaxamento do plasmídeo superenovelado. A inibição da enzima hTopoIB em concentrações próximas ao IC50, mesmo de forma parcial, pelos complexos fornece indícios que a enzima Topo-IB pode ser considerada como um dos possíveis alvos biológicos. Entre os complexos avaliados em células HEK293T-uGFP, o composto AMP5 foi um inibidor da atividade quimiotripsina-like do proteassomo 26S em células viáveis, indicando que a enzima é alvo biológico.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES: código de financiamento - 001porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessComplexo rutênioDNAHSAInibição proteassomaTopoisomeraseCâncer de mamaCâncer de pulmãoLinhagem tumoral A549Linhagem tumoral MDA-MB-231MCF-10AMRC-5RMN de 31P2-difenilfosfinapiridinaDPPBCIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::CAMPOS DE COORDENACAOCIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICAAvaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureiasEvaluation of the cytotoxic activity of new Ru(II)-phosphine complexes with mercapto or acylthiourea ligandsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTese Gabriel H. Ribeiro - Homologada.pdfTese Gabriel H. Ribeiro - Homologada.pdfTese Gabriel H. Ribeiro - Homologadaapplication/pdf18023467https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/14319/1/Tese%20Gabriel%20H.%20Ribeiro%20-%20Homologada.pdf28afb6462935712eb0d1d7370ad08faaMD51Homologação tese - Carta comprovante da versão final de tese.pdfHomologação tese - Carta comprovante da versão final de tese.pdfCarta comprovante da versão final de tese orientadorapplication/pdf324459https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/14319/2/Homologa%c3%a7%c3%a3o%20tese%20-%20Carta%20comprovante%20da%20vers%c3%a3o%20final%20de%20tese.pdf2f8ab6fe0c2be35873b70a5371c551ebMD52CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/14319/3/license_rdfe39d27027a6cc9cb039ad269a5db8e34MD53TEXTTese Gabriel H. Ribeiro - Homologada.pdf.txtTese Gabriel H. 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dc.title.por.fl_str_mv |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias |
dc.title.alternative.eng.fl_str_mv |
Evaluation of the cytotoxic activity of new Ru(II)-phosphine complexes with mercapto or acylthiourea ligands |
title |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias |
spellingShingle |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias Ribeiro, Gabriel Henrique Complexo rutênio DNA HSA Inibição proteassoma Topoisomerase Câncer de mama Câncer de pulmão Linhagem tumoral A549 Linhagem tumoral MDA-MB-231 MCF-10A MRC-5 RMN de 31P 2-difenilfosfinapiridina DPPB CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::CAMPOS DE COORDENACAO CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICA |
title_short |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias |
title_full |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias |
title_fullStr |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias |
title_full_unstemmed |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias |
title_sort |
Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias |
author |
Ribeiro, Gabriel Henrique |
author_facet |
Ribeiro, Gabriel Henrique |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/3701616795598511 |
dc.contributor.author.fl_str_mv |
Ribeiro, Gabriel Henrique |
dc.contributor.advisor1.fl_str_mv |
Batista, Alzir Azevedo |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6469642481998660 |
contributor_str_mv |
Batista, Alzir Azevedo |
dc.subject.por.fl_str_mv |
Complexo rutênio DNA HSA Inibição proteassoma Topoisomerase Câncer de mama Câncer de pulmão Linhagem tumoral A549 Linhagem tumoral MDA-MB-231 MCF-10A MRC-5 RMN de 31P 2-difenilfosfinapiridina DPPB |
topic |
Complexo rutênio DNA HSA Inibição proteassoma Topoisomerase Câncer de mama Câncer de pulmão Linhagem tumoral A549 Linhagem tumoral MDA-MB-231 MCF-10A MRC-5 RMN de 31P 2-difenilfosfinapiridina DPPB CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::CAMPOS DE COORDENACAO CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::CAMPOS DE COORDENACAO CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA::QUIMICA BIO-INORGANICA |
description |
In this thesis, two series of new Ru-phosphine complexes containing mercapto or acylthiourea ligands were synthesized, characterized and assessed their cytotoxic activities. The first series is composed of five complexes of general formula [Ru(NS)(dphppy)(dppb)]PF6 (AMP1-AMP5) [dpphpy = diphenyl-2-pyridylphosphine, NS = 2-mercaptopyridine (pyS; AMP1), 2-thiazoline-2-thiol (tzdt; AMP2), 6-mercaptopyridine-3-carboxylic acid (mpca, AMP3), 2-mercaptopyrimidine (pySm, AMP4) and 4,6-diamino-2-mercaptopyrimidine (damp, AMP5); dppb = 1,4-bis(diphenylphosphino)butane]. In the second series, complexes present the general formula [Ru(OS)(dphppy)(dppb)]PF6 (SPPM2-SPPM6) [OS= N,N-(dimethyl)-N'-benzoylthiourea (dmbth; SPPM2), N, N-(diethyl)-N'-benzoylthiourea (debth, SPPM3), N,N-(dipropyl)-N'-benzoylthiourea (SPPM4), N,N-(dibutyl)-N'-benzoylthiourea (dbbth, SPPM5), N,N-(diphenyl)-N'-benzoylthiourea (dpbth, SPPM6)]. The complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV/Visible, 1D and 2D NMR) and X-ray diffraction. In the characterization, the correlation between the phosphorous atoms with their respective aromatic hydrogens of the compounds in the assignment stands out, by 1H-31P HMBC experiments. The cytotoxic activity of the complexes was evaluated against cell lines derived from human tumors, MDA-MB-231 (breast cancer) and A549 (lung cancer) and against non-tumoral human cell lines derived from lung MCR-5 and breast MCF-10A. The compounds showed good to excellent anticancer activities against cancer cell lines, with IC50 values significantly lower than the free ligands and cisplatin. For A549 tumor cells, the complexes with mercaptos had IC50 values in the range of 0.12-2.59 µM, and the complexes with acylthiourea in the range of 0.10-0.98 µM. In the breast tumor cells, IC50 values were in the range of 0.08-0.36 µM and 0.25-1.05 µM for the AMP and SPPM series, respectively. All complexes were also selective for tumor cells in comparison to the respective non-tumoral cell lines. The complexes with acylthiourea showed expressive selectivity toward lung tumor cells, with selectivity indexes (SI) values above (or equal to) 10. The compounds AMP4 (SI= 6.7) and SPPM4 (SI= 33) were chosen for further studies in lung tumor cells, due to the better selectivity index in their respective series. Both complexes were able to inhibit colony formation and alter the morphology of tumor cells A549. In the cell cycle analysis of the cells, the complexes induced an accumulation of cells with abnormal content, called Sub-G1 cells, which represents the fraction of dead cells and fragmented DNA. The fragmentation of DNA is due to the cell apoptosis process, confirmed for cells treated with the AMP4. For A549 cells treated with the SPPM4 complex, possibly other cell death processes are involved. The possible biological targets of the complexes that could act as triggers for the cell death process were also studied. The complexes presented weak reversible interactions via minor groove of the DNA. The complexes caused no significant changes in the tertiary and secondary DNA structures, indicating that this biomolecule is probably not the primary target for them. Study with enzymatic target, especially targets overexpressed in tumor cells that justify the cytotoxic activity of the compounds were carried out. And it was found that the complexes are capable of partially inhibiting the Top IB catalytic activity, at low concentrations, close to the IC50 values of cancer cell lines. Overall, the proteasome enzyme can be a biological target for these complexes. The results indicate that ruthenium complexes containing mercaptos or acylthiourea present promising cytotoxic activities for the development of chemotherapeutics for the treatment of cancer. Among the complexes assayed in HEK293T-uGFP cells, complex AMP5 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent, indicating that the proteasome 26S enzyme can be a biological target of the compound. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-12-11 |
dc.date.accessioned.fl_str_mv |
2021-05-27T11:30:55Z |
dc.date.available.fl_str_mv |
2021-05-27T11:30:55Z |
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 |
RIBEIRO, Gabriel Henrique. Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias. 2020. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2020. Disponível em: https://repositorio.ufscar.br/handle/ufscar/14319. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/14319 |
identifier_str_mv |
RIBEIRO, Gabriel Henrique. Avaliação da atividade citotóxica de complexos fosfínicos de Ru(II) com ligantes mercaptos e aciltioureias. 2020. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2020. Disponível em: https://repositorio.ufscar.br/handle/ufscar/14319. |
url |
https://repositorio.ufscar.br/handle/ufscar/14319 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ |
eu_rights_str_mv |
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 |
publisher.none.fl_str_mv |
Universidade Federal de São Carlos Câmpus São Carlos |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFSCAR instname:Universidade Federal de São Carlos (UFSCAR) instacron:UFSCAR |
instname_str |
Universidade Federal de São Carlos (UFSCAR) |
instacron_str |
UFSCAR |
institution |
UFSCAR |
reponame_str |
Repositório Institucional da UFSCAR |
collection |
Repositório Institucional da UFSCAR |
bitstream.url.fl_str_mv |
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repository.name.fl_str_mv |
Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR) |
repository.mail.fl_str_mv |
|
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1777472137206956032 |