Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos

Detalhes bibliográficos
Autor(a) principal: RODRIGUES, Wanderson Barros
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFMA
Texto Completo: https://tedebc.ufma.br/jspui/handle/tede/tede/4143
Resumo: Cancer is a group of multifactorial diseases arising from genetic mutations caused by chemical substances, viral infections, radiation exposure, inflammatory diseases resulting from infection, autoimmune diseases or inherited from the progenitor line. Although platinum-based organometallic complexes are used as first-line drugs in the fight against cancer, they cause a number of problems as serious side effects, including nephrotoxicity, neurotoxicity and ototoxicity. In this sense, new studies with copper-based metal complexes appear, they present a lower toxicity, a greater spectrum of action and can be effective against tumors resistant to the standard treatment with cisplatin. Thus, this work evaluated the antitumor activity in vitro of organometallic complexes of Phenanthroline associated with copper (II) and amino acids, their interaction with DNA molecules in silico and predict their pharmacokinetic properties from in silico studies. Human cancer cell lines HL- 60, PC-3 and SNB-19 and the non-tumor line RAW 264.7 (murine macrophage) were used. Cytotoxicity was assessed using the MTT assay after 72-hour exposure of the cells to the CuPhG and CuPhS complexes. Then, molecular Docking was performed to observe the affinity with the possible target. Finally, the prediction of the pharmacokinetic parameters of copper (II) complexes was carried out, including physical-chemical parameters, pharmacokinetic profile (ADME) and toxicity. The cytotoxicity evaluated by the MTT reduction method showed that the CuPhG and CuPhS complexes showed cytotoxic activity for all strains evaluated. The results of molecular docking of the CuPhG and CuPhS ligands show that the complexes are interspersed with the DNA grooves and have good molecular affinity with the targets. In addition, the pharmacokinetic prediction indicates that complexes have advantageous properties such as less interaction with Cytochrome P450 and P glycoproteins. Both complexes were shown to have antitumor activity, however the CuPhS complex was more selective for tumor cells when compared to the CuPhG complex.
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spelling REIS, Aramys Silva doshttp://lattes.cnpq.br/1040580590566490ROCHA, Jefferson Almeidahttp://lattes.cnpq.br/7613552342859114REIS, Aramys Silva doshttp://lattes.cnpq.br/1040580590566490ROCHA, Jefferson Almeidahttp://lattes.cnpq.br/7613552342859114PEREIRA, Paulo Vitor Soeirohttp://lattes.cnpq.br/7281767698416958LAGE, Mateus Ribeirohttp://lattes.cnpq.br/7180752938220497http://lattes.cnpq.br/3860106597086603RODRIGUES, Wanderson Barros2022-10-11T12:47:17Z2021-09-16RODRIGUES, Wanderson Barros. Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos. 2021. 76 f. Dissertação (Programa de Pós-Graduação em Saúde e Tecnologia) - Universidade Federal do Maranhão, Imperatriz.https://tedebc.ufma.br/jspui/handle/tede/tede/4143Cancer is a group of multifactorial diseases arising from genetic mutations caused by chemical substances, viral infections, radiation exposure, inflammatory diseases resulting from infection, autoimmune diseases or inherited from the progenitor line. Although platinum-based organometallic complexes are used as first-line drugs in the fight against cancer, they cause a number of problems as serious side effects, including nephrotoxicity, neurotoxicity and ototoxicity. In this sense, new studies with copper-based metal complexes appear, they present a lower toxicity, a greater spectrum of action and can be effective against tumors resistant to the standard treatment with cisplatin. Thus, this work evaluated the antitumor activity in vitro of organometallic complexes of Phenanthroline associated with copper (II) and amino acids, their interaction with DNA molecules in silico and predict their pharmacokinetic properties from in silico studies. Human cancer cell lines HL- 60, PC-3 and SNB-19 and the non-tumor line RAW 264.7 (murine macrophage) were used. Cytotoxicity was assessed using the MTT assay after 72-hour exposure of the cells to the CuPhG and CuPhS complexes. Then, molecular Docking was performed to observe the affinity with the possible target. Finally, the prediction of the pharmacokinetic parameters of copper (II) complexes was carried out, including physical-chemical parameters, pharmacokinetic profile (ADME) and toxicity. The cytotoxicity evaluated by the MTT reduction method showed that the CuPhG and CuPhS complexes showed cytotoxic activity for all strains evaluated. The results of molecular docking of the CuPhG and CuPhS ligands show that the complexes are interspersed with the DNA grooves and have good molecular affinity with the targets. In addition, the pharmacokinetic prediction indicates that complexes have advantageous properties such as less interaction with Cytochrome P450 and P glycoproteins. Both complexes were shown to have antitumor activity, however the CuPhS complex was more selective for tumor cells when compared to the CuPhG complex.O câncer é um grupo de doenças multifatoriais oriundas de mutações genéticas provocadas por substâncias químicas, infecções virais, exposição à radiação, doenças inflamatórias resultantes de infecção, doenças autoimunes ou herdadas da linhagem progenitora. Embora os complexos organometálicos a base de platina sejam usados como fármacos de primeira linha no combate ao câncer, eles acarretam uma série de problemas como efeitos colaterais graves, incluindo nefrotoxicidade, neurotoxicidade e ototoxicidade. Nesse sentido, surgem novos estudos com complexos metálicos a base de cobre, esses apresentam uma menor toxicidade, maior espectro de ação e podem ser eficazes contra tumores resistentes ao tratamento padrão com cisplatina. Assim, esse trabalho avaliou a atividade antitumoral in vitro de complexos organometálicos de fenantrolina associado com cobre (II) e aminoácidos, sua interação com moléculas de DNA in silico e realizou predição das suas propriedades farmacocinéticas a partir de estudos in silico. Foram utilizadas linhagens celulares de cânceres humanos HL-60, PC-3 e SNB-19 e a linhagem não tumoral RAW 264.7 (macrófago murino). A citotoxicidade foi avaliada usando o ensaio MTT, após exposição das células aos complexos CuPhG e CuPhS por 72 horas. Em seguida, foi realizado o docking molecular para observar a afinidade com o possível alvo. Por último, foi realizada a predição dos parâmetros farmacocinéticos dos complexos de cobre (II), incluindo parâmetros físico-químicos, perfil farmacocinético (ADME) e toxicidade. A citotoxicidade avaliada pelo método de redução do MTT mostrou que os complexos CuPhG e CuPhS apresentaram atividade citotóxica para todas as linhagens avaliadas. Os resultados de docking molecular dos ligantes CuPhG e CuPhS mostraram que os complexos se intercalam com os sulcos de DNA e apresentam boa afinidade molecular com os alvos. Além disso, a predição farmacocinética indica que os complexos possuem propriedades vantajosas, como menor interação com os citocromos P450 e com as glicoproteínas P. Ambos os complexos mostraram ter atividade antitumoral, contudo o complexo CuPhS se mostrou mais seletivo para as células tumorais quando comparado com o complexo CuPhG.Submitted by Jonathan Sousa de Almeida (jonathan.sousa@ufma.br) on 2022-10-11T12:47:17Z No. of bitstreams: 1 WANDERSONBARROSRODRIGUES.pdf: 757471 bytes, checksum: 4303f7e2a74a8d199e7b9c5c17373591 (MD5)Made available in DSpace on 2022-10-11T12:47:17Z (GMT). No. of bitstreams: 1 WANDERSONBARROSRODRIGUES.pdf: 757471 bytes, checksum: 4303f7e2a74a8d199e7b9c5c17373591 (MD5) Previous issue date: 2021-09-16FAPEMAapplication/pdfporUniversidade Federal do MaranhãoPROGRAMA DE PÓS-GRADUAÇÃO EM SAÚDE E TECNOLOGIAUFMABrasilCOORDENAÇÃO DO CURSO DE MEDICINA IMPERATRIZ/CCSSTcomplexos organometálicos;atividade antitumoral;cobre;Docking Molecular.organometallic complexes;antitumor activity;copper;Molecular Docking.CancerologiaCiências da SaúdeDeterminação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidosDetermination of the antitumor activity of copper (II) complexes associated with phenanthroline and amino acidsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFMAinstname:Universidade Federal do Maranhão (UFMA)instacron:UFMAORIGINALWANDERSONBARROSRODRIGUES.pdfWANDERSONBARROSRODRIGUES.pdfapplication/pdf757471http://tedebc.ufma.br:8080/bitstream/tede/4143/2/WANDERSONBARROSRODRIGUES.pdf4303f7e2a74a8d199e7b9c5c17373591MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82255http://tedebc.ufma.br:8080/bitstream/tede/4143/1/license.txt97eeade1fce43278e63fe063657f8083MD51tede/41432022-10-11 09:47:17.974oai:tede2: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Biblioteca Digital de Teses e Dissertaçõeshttps://tedebc.ufma.br/jspui/PUBhttp://tedebc.ufma.br:8080/oai/requestrepositorio@ufma.br||repositorio@ufma.bropendoar:21312022-10-11T12:47:17Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA)false
dc.title.por.fl_str_mv Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
dc.title.alternative.eng.fl_str_mv Determination of the antitumor activity of copper (II) complexes associated with phenanthroline and amino acids
title Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
spellingShingle Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
RODRIGUES, Wanderson Barros
complexos organometálicos;
atividade antitumoral;
cobre;
Docking Molecular.
organometallic complexes;
antitumor activity;
copper;
Molecular Docking.
Cancerologia
Ciências da Saúde
title_short Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
title_full Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
title_fullStr Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
title_full_unstemmed Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
title_sort Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos
author RODRIGUES, Wanderson Barros
author_facet RODRIGUES, Wanderson Barros
author_role author
dc.contributor.advisor1.fl_str_mv REIS, Aramys Silva dos
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1040580590566490
dc.contributor.advisor-co1.fl_str_mv ROCHA, Jefferson Almeida
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/7613552342859114
dc.contributor.referee1.fl_str_mv REIS, Aramys Silva dos
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/1040580590566490
dc.contributor.referee2.fl_str_mv ROCHA, Jefferson Almeida
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/7613552342859114
dc.contributor.referee3.fl_str_mv PEREIRA, Paulo Vitor Soeiro
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/7281767698416958
dc.contributor.referee4.fl_str_mv LAGE, Mateus Ribeiro
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/7180752938220497
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/3860106597086603
dc.contributor.author.fl_str_mv RODRIGUES, Wanderson Barros
contributor_str_mv REIS, Aramys Silva dos
ROCHA, Jefferson Almeida
REIS, Aramys Silva dos
ROCHA, Jefferson Almeida
PEREIRA, Paulo Vitor Soeiro
LAGE, Mateus Ribeiro
dc.subject.por.fl_str_mv complexos organometálicos;
atividade antitumoral;
cobre;
Docking Molecular.
topic complexos organometálicos;
atividade antitumoral;
cobre;
Docking Molecular.
organometallic complexes;
antitumor activity;
copper;
Molecular Docking.
Cancerologia
Ciências da Saúde
dc.subject.eng.fl_str_mv organometallic complexes;
antitumor activity;
copper;
Molecular Docking.
dc.subject.cnpq.fl_str_mv Cancerologia
Ciências da Saúde
description Cancer is a group of multifactorial diseases arising from genetic mutations caused by chemical substances, viral infections, radiation exposure, inflammatory diseases resulting from infection, autoimmune diseases or inherited from the progenitor line. Although platinum-based organometallic complexes are used as first-line drugs in the fight against cancer, they cause a number of problems as serious side effects, including nephrotoxicity, neurotoxicity and ototoxicity. In this sense, new studies with copper-based metal complexes appear, they present a lower toxicity, a greater spectrum of action and can be effective against tumors resistant to the standard treatment with cisplatin. Thus, this work evaluated the antitumor activity in vitro of organometallic complexes of Phenanthroline associated with copper (II) and amino acids, their interaction with DNA molecules in silico and predict their pharmacokinetic properties from in silico studies. Human cancer cell lines HL- 60, PC-3 and SNB-19 and the non-tumor line RAW 264.7 (murine macrophage) were used. Cytotoxicity was assessed using the MTT assay after 72-hour exposure of the cells to the CuPhG and CuPhS complexes. Then, molecular Docking was performed to observe the affinity with the possible target. Finally, the prediction of the pharmacokinetic parameters of copper (II) complexes was carried out, including physical-chemical parameters, pharmacokinetic profile (ADME) and toxicity. The cytotoxicity evaluated by the MTT reduction method showed that the CuPhG and CuPhS complexes showed cytotoxic activity for all strains evaluated. The results of molecular docking of the CuPhG and CuPhS ligands show that the complexes are interspersed with the DNA grooves and have good molecular affinity with the targets. In addition, the pharmacokinetic prediction indicates that complexes have advantageous properties such as less interaction with Cytochrome P450 and P glycoproteins. Both complexes were shown to have antitumor activity, however the CuPhS complex was more selective for tumor cells when compared to the CuPhG complex.
publishDate 2021
dc.date.issued.fl_str_mv 2021-09-16
dc.date.accessioned.fl_str_mv 2022-10-11T12:47:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv RODRIGUES, Wanderson Barros. Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos. 2021. 76 f. Dissertação (Programa de Pós-Graduação em Saúde e Tecnologia) - Universidade Federal do Maranhão, Imperatriz.
dc.identifier.uri.fl_str_mv https://tedebc.ufma.br/jspui/handle/tede/tede/4143
identifier_str_mv RODRIGUES, Wanderson Barros. Determinação da atividade antitumoral de complexos de cobre (II) associado com fenantrolina e aminoácidos. 2021. 76 f. Dissertação (Programa de Pós-Graduação em Saúde e Tecnologia) - Universidade Federal do Maranhão, Imperatriz.
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dc.publisher.none.fl_str_mv Universidade Federal do Maranhão
dc.publisher.program.fl_str_mv PROGRAMA DE PÓS-GRADUAÇÃO EM SAÚDE E TECNOLOGIA
dc.publisher.initials.fl_str_mv UFMA
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv COORDENAÇÃO DO CURSO DE MEDICINA IMPERATRIZ/CCSST
publisher.none.fl_str_mv Universidade Federal do Maranhão
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