Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/4437 |
Resumo: | It is well known that metal complexes have been used as therapeutic agents since ancient times. However, with the success of cisplatin development as an antitumor agent in 1960inorganic drugs come to mainstream again. Despite the success of platinum compounds, serious problems are encountered when administering these drugs, such as nephrotoxicity, neurotoxicity and acquired resistance. In face of these problems other chemotherapeutic agents, less toxic to the organism and more efficient, become necessary. Several studies have been shown that ruthenium compounds present high selectivity for tumor cells and low systemic toxicity when compared to platinum (II) compounds. The present study evaluate antimor activity of two new ruthenium(II) compounds associated with amino acids, alanine and tryptophan. Ruthenium(II) compound were tested against B16-F10 and Ehrlich tumor cell lines and L-929 basal line using MTT assay, at different concentrations (0.2 - 200 mM) for 48 hours of treatment. Cell cycle analysis and apoptosis induction analyses by flow citometry and comet assay for DNA damage were also performed The IC50 values were estimated as 16.17 mM (RuAla) and 7.75 mM (RuTrp). The compound RuAla proved to be specific for the B16-F10 tumor cell line and showed a significant ability to change cell cycling profiles, arresting cells inG0/G1 phase, and also inducing cell death by apoptosis within 48 hours of treatment. The compound RuTrp showed high cytotoxic potential against Ehrlich tumor, interfering cell cycle kinetics,causing cell cycle arrest in G0/G1 phase and inducing cell death by apoptosis. Comet assay presented damage to genetic material only when cells were trated with high concentrations of RuTrp. , RuAla and RuTrp presented relevant cytotoxic activities towards tumor lineages tested in vitro. Thus, more specific tests are needed to elucidate the mechanism of action of these promising The ruthenium(II) compounds. |
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Lacerda, Elisângela de Paula Silveirahttp://lattes.cnpq.br/9390789693192751Lacerda, Elisângela de Paula SilveiraBatista, Alzir AzevedoCortez, Alane Pereirahttp://lattes.cnpq.br/4558919566544432Porto, Hellen Karine Paes2015-04-22T16:44:43Z2012-02-24PORTO, H. K. P. Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas. 2012. 95 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2012.http://repositorio.bc.ufg.br/tede/handle/tede/4437It is well known that metal complexes have been used as therapeutic agents since ancient times. However, with the success of cisplatin development as an antitumor agent in 1960inorganic drugs come to mainstream again. Despite the success of platinum compounds, serious problems are encountered when administering these drugs, such as nephrotoxicity, neurotoxicity and acquired resistance. In face of these problems other chemotherapeutic agents, less toxic to the organism and more efficient, become necessary. Several studies have been shown that ruthenium compounds present high selectivity for tumor cells and low systemic toxicity when compared to platinum (II) compounds. The present study evaluate antimor activity of two new ruthenium(II) compounds associated with amino acids, alanine and tryptophan. Ruthenium(II) compound were tested against B16-F10 and Ehrlich tumor cell lines and L-929 basal line using MTT assay, at different concentrations (0.2 - 200 mM) for 48 hours of treatment. Cell cycle analysis and apoptosis induction analyses by flow citometry and comet assay for DNA damage were also performed The IC50 values were estimated as 16.17 mM (RuAla) and 7.75 mM (RuTrp). The compound RuAla proved to be specific for the B16-F10 tumor cell line and showed a significant ability to change cell cycling profiles, arresting cells inG0/G1 phase, and also inducing cell death by apoptosis within 48 hours of treatment. The compound RuTrp showed high cytotoxic potential against Ehrlich tumor, interfering cell cycle kinetics,causing cell cycle arrest in G0/G1 phase and inducing cell death by apoptosis. Comet assay presented damage to genetic material only when cells were trated with high concentrations of RuTrp. , RuAla and RuTrp presented relevant cytotoxic activities towards tumor lineages tested in vitro. Thus, more specific tests are needed to elucidate the mechanism of action of these promising The ruthenium(II) compounds.Sabe-se que complexos metálicos têm sido usados como agentes terapêuticos desde a antiguidade. No entanto, o reaparecimento de drogas inorgânicas iniciou-se em 1960 com o desenvolvimento e o sucesso da cisplatina como agente antitumoral. Apesar do sucesso dos compostos de platina, sérios problemas são enfrentados durante a administração dessas drogas, como nefro e neurotoxicidade e resistência. Em vista dos problemas relacionados com o tratamento a base de platina, outros quimioterápicos que sejam menos tóxicos ao organismo e mais eficientes tornam-se necessários. O estudo da atividade antitumoral se destaca com os complexos de rutênio, os quais têm demonstrado alta seletividade para células tumorais e baixa toxicidade sistêmica, quando comparados aos compostos de platina (II). O presente estudo teve como objetivo avaliar dois novos compostos de Rutênio (II), associados a aminoácidos, Alanina e Triptofano, com potencial antitumoral. No ensaio de citotoxicidade, os dois complexos de Rutênio foram avaliados frente a duas linhagens tumorais (B16-F10, Tumor de Ehrlich) e uma linhagem basal (L-929) através do teste de MTT, em diferentes concentrações dos compostos (0,2 – 200 μM) por 48 horas de tratamento. Foram realizados também análises de ciclo celular, ensaio cometa e teste Anexina V para avaliação do mecanismo de morte. Análise estatística para comparação entre os grupos tratados e controle foi utilizado Anova segundo um único critério e pós-teste Dunnet’s (software GraphPad Prism V4). Os valores de IC50 estimados foram 16,17μM (RuAla) e 7,75μM (RuTrp). O composto RuAla mostrou-se específico para a linhagem B16-F10 e apresentou capacidade de alterar o ciclo celular das células, parando a ciclagem em fase G0/G1, e também demonstrou induzir morte celular por apoptose em 48 horas de tratamento. O composto RuTrp apresentou alto potencial citotóxico frente ao Tumor de Ehrlich, interferiu na cinética do ciclo celular, parando o ciclo celular em fase G0/G1. O RuTrp também induziu morte celular por apoptose, entretanto somente apresentou dano ao material genético em altas concentrações. Todavia, teste mais específicos são necessários para a elucidação do mecanismo de ação desses dois novos composto a base de Rutênio (II) com promissores resultados anti-câncer.Submitted by Luanna Matias (lua_matias@yahoo.com.br) on 2015-04-22T16:40:18Z No. of bitstreams: 2 Dissertação - Hellen Karine Paes Porto - 2012.pdf: 3126397 bytes, checksum: db30e536f55c8163ffbd3cd680c86ca9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luanna Matias (lua_matias@yahoo.com.br) on 2015-04-22T16:44:43Z (GMT) No. of bitstreams: 2 Dissertação - Hellen Karine Paes Porto - 2012.pdf: 3126397 bytes, checksum: db30e536f55c8163ffbd3cd680c86ca9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2015-04-22T16:44:43Z (GMT). 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dc.title.por.fl_str_mv |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas |
title |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas |
spellingShingle |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas Porto, Hellen Karine Paes Rutênio Câncer B16-F10 Tumor de Ehrlich Citotoxicidade Apoptose Ruthenium Cancer Ehrlich tumor Cytotoxicity Apoptosis CLINICA MEDICA::CANCEROLOGIA |
title_short |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas |
title_full |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas |
title_fullStr |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas |
title_full_unstemmed |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas |
title_sort |
Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas |
author |
Porto, Hellen Karine Paes |
author_facet |
Porto, Hellen Karine Paes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Lacerda, Elisângela de Paula Silveira |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9390789693192751 |
dc.contributor.referee1.fl_str_mv |
Lacerda, Elisângela de Paula Silveira |
dc.contributor.referee2.fl_str_mv |
Batista, Alzir Azevedo |
dc.contributor.referee3.fl_str_mv |
Cortez, Alane Pereira |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4558919566544432 |
dc.contributor.author.fl_str_mv |
Porto, Hellen Karine Paes |
contributor_str_mv |
Lacerda, Elisângela de Paula Silveira Lacerda, Elisângela de Paula Silveira Batista, Alzir Azevedo Cortez, Alane Pereira |
dc.subject.por.fl_str_mv |
Rutênio Câncer B16-F10 Tumor de Ehrlich Citotoxicidade Apoptose |
topic |
Rutênio Câncer B16-F10 Tumor de Ehrlich Citotoxicidade Apoptose Ruthenium Cancer Ehrlich tumor Cytotoxicity Apoptosis CLINICA MEDICA::CANCEROLOGIA |
dc.subject.eng.fl_str_mv |
Ruthenium Cancer Ehrlich tumor Cytotoxicity Apoptosis |
dc.subject.cnpq.fl_str_mv |
CLINICA MEDICA::CANCEROLOGIA |
description |
It is well known that metal complexes have been used as therapeutic agents since ancient times. However, with the success of cisplatin development as an antitumor agent in 1960inorganic drugs come to mainstream again. Despite the success of platinum compounds, serious problems are encountered when administering these drugs, such as nephrotoxicity, neurotoxicity and acquired resistance. In face of these problems other chemotherapeutic agents, less toxic to the organism and more efficient, become necessary. Several studies have been shown that ruthenium compounds present high selectivity for tumor cells and low systemic toxicity when compared to platinum (II) compounds. The present study evaluate antimor activity of two new ruthenium(II) compounds associated with amino acids, alanine and tryptophan. Ruthenium(II) compound were tested against B16-F10 and Ehrlich tumor cell lines and L-929 basal line using MTT assay, at different concentrations (0.2 - 200 mM) for 48 hours of treatment. Cell cycle analysis and apoptosis induction analyses by flow citometry and comet assay for DNA damage were also performed The IC50 values were estimated as 16.17 mM (RuAla) and 7.75 mM (RuTrp). The compound RuAla proved to be specific for the B16-F10 tumor cell line and showed a significant ability to change cell cycling profiles, arresting cells inG0/G1 phase, and also inducing cell death by apoptosis within 48 hours of treatment. The compound RuTrp showed high cytotoxic potential against Ehrlich tumor, interfering cell cycle kinetics,causing cell cycle arrest in G0/G1 phase and inducing cell death by apoptosis. Comet assay presented damage to genetic material only when cells were trated with high concentrations of RuTrp. , RuAla and RuTrp presented relevant cytotoxic activities towards tumor lineages tested in vitro. Thus, more specific tests are needed to elucidate the mechanism of action of these promising The ruthenium(II) compounds. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-02-24 |
dc.date.accessioned.fl_str_mv |
2015-04-22T16:44:43Z |
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 |
PORTO, H. K. P. Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas. 2012. 95 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/4437 |
identifier_str_mv |
PORTO, H. K. P. Avaliação do potencial antitumoral de dois novos complexos de rutênio (II) contendo alanina e triptofano em suas estruturas. 2012. 95 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2012. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/4437 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
824936988196152412 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 |
dc.relation.department.fl_str_mv |
6010281161524209375 |
dc.relation.cnpq.fl_str_mv |
-1267568703726780453 |
dc.relation.sponsorship.fl_str_mv |
2075167498588264571 -2555911436985713659 |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Ciências Farmacêuticas (FF) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade Farmácia - FF (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
instname_str |
Universidade Federal de Goiás (UFG) |
instacron_str |
UFG |
institution |
UFG |
reponame_str |
Repositório Institucional da UFG |
collection |
Repositório Institucional da UFG |
bitstream.url.fl_str_mv |
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bitstream.checksum.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tasesdissertacoes.bc@ufg.br |
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1798044427843796992 |