Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo

Detalhes bibliográficos
Ano de defesa: 2022
Autor(a) principal: Nascimento, Juliana Sales do
Orientador(a): Holanda, Alda Karine Medeiros
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
DNA
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/73354
Resumo: The cis-[Fe(cyclam)Cl2]Cl (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex reacts with quinizarin (1,4-dihydroxy-9,10-anthraquinone, Qz), a biologically relevant molecule, yielding the binuclear complex [(Fe(cyclam))2(Qz)]Cl(PF6)3. This new compound was characterized by means of elemental analysis, X-ray diffraction, cyclic voltammetry and spectroscopic techniques. Crystallographic and FTIR data indicated that the bridging ligand, quinizarin, is coordinated to the FeIII cation via the oxygen atoms of the carbonyl groups in the form of quinones. The effect of ancillary (cyclam) and bridging (Qz) ligands on the properties of the complex is reflected by the stabilization of the FeIII–FeIII configuration supported by Mössbauer spectroscopy. The efficiency of Oxigen-reactive species generation and DNA cleavage activity for this binuclear complex, as well as for the free quinizarin ligand, were investigated. This metal complex exhibited very low photochemical activity; however, it revealed a great ability to cleave the DNA molecule in the presence of glutathione, which was associated with the production of Oxigen-reactive species species. Thereafter, the cytotoxic activity of these compounds was evaluated using the MTS assay against human tumor cells, namely lung adenocarcinoma (A549) and prostate carcinoma (LNCaP clone FGC), and against normal fibroblasts (L929). Our findings indicated low cytotoxic effects in general, where only a slight reduction in A549 and L929 cell viability was observed after light irradiation. Despite the lack of any significant biological activity, this binuclear compound validates in vitro the essential role of metal binding to an anthracycline-like moiety in the generation of Oxigen-reactive species. The latter may be responsible for some of the cardiotoxicity reported for anthracycline-based drug.
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spelling Nascimento, Juliana Sales doHolanda, Alda Karine Medeiros2023-07-05T17:44:03Z2023-07-05T17:44:03Z2022NASCIMENTO, Juliana Sales do. Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo. 2022. 81 f. Dissertação (Mestrado em Química Inorgânica) - Universidade Federal do Ceará, Fortaleza, 2022.http://www.repositorio.ufc.br/handle/riufc/73354The cis-[Fe(cyclam)Cl2]Cl (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex reacts with quinizarin (1,4-dihydroxy-9,10-anthraquinone, Qz), a biologically relevant molecule, yielding the binuclear complex [(Fe(cyclam))2(Qz)]Cl(PF6)3. This new compound was characterized by means of elemental analysis, X-ray diffraction, cyclic voltammetry and spectroscopic techniques. Crystallographic and FTIR data indicated that the bridging ligand, quinizarin, is coordinated to the FeIII cation via the oxygen atoms of the carbonyl groups in the form of quinones. The effect of ancillary (cyclam) and bridging (Qz) ligands on the properties of the complex is reflected by the stabilization of the FeIII–FeIII configuration supported by Mössbauer spectroscopy. The efficiency of Oxigen-reactive species generation and DNA cleavage activity for this binuclear complex, as well as for the free quinizarin ligand, were investigated. This metal complex exhibited very low photochemical activity; however, it revealed a great ability to cleave the DNA molecule in the presence of glutathione, which was associated with the production of Oxigen-reactive species species. Thereafter, the cytotoxic activity of these compounds was evaluated using the MTS assay against human tumor cells, namely lung adenocarcinoma (A549) and prostate carcinoma (LNCaP clone FGC), and against normal fibroblasts (L929). Our findings indicated low cytotoxic effects in general, where only a slight reduction in A549 and L929 cell viability was observed after light irradiation. Despite the lack of any significant biological activity, this binuclear compound validates in vitro the essential role of metal binding to an anthracycline-like moiety in the generation of Oxigen-reactive species. The latter may be responsible for some of the cardiotoxicity reported for anthracycline-based drug.O complexo cis-[Fe(cyclam)Cl2]Cl (cyclam = 1,4,8,11-tetraazaciclotetradecano) reage com quinizarina (1,4-dihidroxi-9,10-antraquinona, Qz), uma molécula biologicamente relevante, produzindo o complexo binuclear [(Fe(cyclama))2(Qz)]Cl(PF6)3. Este novo composto foi caracterizado por meio de análise elementar, difração de raios-X, voltametria cíclica e técnicas espectroscópicas. Os dados cristalográficos e FTIR indicaram que o ligante em ponte, quinizarina, é coordenado ao cátion FeIII através dos átomos de oxigênio dos grupos carbonila presente nas quinonas. O efeito dos ligantes auxiliares (cyclam) e do ligante em ponte (Qz) nas propriedades do complexo é refletido pela estabilização da configuração FeIII–FeIII confirmada pela espectroscopia de Mössbauer. A eficiência de geração de espécies reativas de oxigênio e atividade de clivagem de DNA para este complexo binuclear, bem como para o ligante quinizarina livre, foram investigados. Este complexo metálico exibiu atividade fotoquímica muito baixa; no entanto revelou uma grande capacidade de clivar a molécula de DNA na presença de glutationa, que foi associada com a produção de espécies reativas de oxigênio. Em seguida, a atividade citotóxica desses compostos foi avaliada utilizando o ensaio MTS contra células tumorais humanas, nomeadamente adenocarcinoma do pulmão (A549) e carcinoma da próstata (clone LNCaP FGC), e contra fibroblastos normais (L929). Nossos achados indicaram baixa citotoxicidade, onde apenas uma ligeira redução na viabilidade das células A549 e L929 foi observada após a irradiação com luz azul. Apesar da falta de qualquer atividade biológica significativa, este composto binuclear valida in vitro o papel essencial da ligação do metal a uma porção semelhante à antraciclinas na geração de espécies reativas de oxigênio. O último pode ser responsável por parte da cardiotoxicidade relatada para drogas à base de antraciclinasQuinizarinaFerroBinuclearMössbauerDNASíntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismoSynthesis and Characterization of the Compound [(Fe(cyclam))2Qz]Cl(PF6)3 for Simulation of Complexes Formed Between Anthracycline Drugs and FeIII IONS from the Bodyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2022_dis_jsnascimento.pdf2022_dis_jsnascimento.pdfapplication/pdf1708633http://repositorio.ufc.br/bitstream/riufc/73354/5/2022_dis_jsnascimento.pdf8b10f87d71036cd372427f21d3f4d9c8MD55LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/73354/6/license.txt8a4605be74aa9ea9d79846c1fba20a33MD56riufc/733542023-07-05 14:44:45.454oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-07-05T17:44:45Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
dc.title.en.pt_BR.fl_str_mv Synthesis and Characterization of the Compound [(Fe(cyclam))2Qz]Cl(PF6)3 for Simulation of Complexes Formed Between Anthracycline Drugs and FeIII IONS from the Body
title Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
spellingShingle Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
Nascimento, Juliana Sales do
Quinizarina
Ferro
Binuclear
Mössbauer
DNA
title_short Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
title_full Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
title_fullStr Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
title_full_unstemmed Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
title_sort Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo
author Nascimento, Juliana Sales do
author_facet Nascimento, Juliana Sales do
author_role author
dc.contributor.author.fl_str_mv Nascimento, Juliana Sales do
dc.contributor.advisor1.fl_str_mv Holanda, Alda Karine Medeiros
contributor_str_mv Holanda, Alda Karine Medeiros
dc.subject.por.fl_str_mv Quinizarina
Ferro
Binuclear
Mössbauer
DNA
topic Quinizarina
Ferro
Binuclear
Mössbauer
DNA
description The cis-[Fe(cyclam)Cl2]Cl (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex reacts with quinizarin (1,4-dihydroxy-9,10-anthraquinone, Qz), a biologically relevant molecule, yielding the binuclear complex [(Fe(cyclam))2(Qz)]Cl(PF6)3. This new compound was characterized by means of elemental analysis, X-ray diffraction, cyclic voltammetry and spectroscopic techniques. Crystallographic and FTIR data indicated that the bridging ligand, quinizarin, is coordinated to the FeIII cation via the oxygen atoms of the carbonyl groups in the form of quinones. The effect of ancillary (cyclam) and bridging (Qz) ligands on the properties of the complex is reflected by the stabilization of the FeIII–FeIII configuration supported by Mössbauer spectroscopy. The efficiency of Oxigen-reactive species generation and DNA cleavage activity for this binuclear complex, as well as for the free quinizarin ligand, were investigated. This metal complex exhibited very low photochemical activity; however, it revealed a great ability to cleave the DNA molecule in the presence of glutathione, which was associated with the production of Oxigen-reactive species species. Thereafter, the cytotoxic activity of these compounds was evaluated using the MTS assay against human tumor cells, namely lung adenocarcinoma (A549) and prostate carcinoma (LNCaP clone FGC), and against normal fibroblasts (L929). Our findings indicated low cytotoxic effects in general, where only a slight reduction in A549 and L929 cell viability was observed after light irradiation. Despite the lack of any significant biological activity, this binuclear compound validates in vitro the essential role of metal binding to an anthracycline-like moiety in the generation of Oxigen-reactive species. The latter may be responsible for some of the cardiotoxicity reported for anthracycline-based drug.
publishDate 2022
dc.date.issued.fl_str_mv 2022
dc.date.accessioned.fl_str_mv 2023-07-05T17:44:03Z
dc.date.available.fl_str_mv 2023-07-05T17:44:03Z
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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dc.identifier.citation.fl_str_mv NASCIMENTO, Juliana Sales do. Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo. 2022. 81 f. Dissertação (Mestrado em Química Inorgânica) - Universidade Federal do Ceará, Fortaleza, 2022.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/73354
identifier_str_mv NASCIMENTO, Juliana Sales do. Síntese e caracterização do composto [(Fe(cyclam))2Qz]Cl(PF6)3 para simulação dos complexos formados entre as drogas antraciclinas e os íons FeIII provenientes do organismo. 2022. 81 f. Dissertação (Mestrado em Química Inorgânica) - Universidade Federal do Ceará, Fortaleza, 2022.
url http://www.repositorio.ufc.br/handle/riufc/73354
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