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dc.creatorGONÇALVES, Ana Cristina Resende-
dc.creator.Latteshttp://lattes.cnpq.br/1940495119988558por
dc.contributor.advisor1MAIA , Pedro Ivo da Silva-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/9442826065341422por
dc.contributor.advisor-co1GUERRA, Wendellpor
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/8904957949852036por
dc.date.accessioned2018-04-13T14:04:55Z-
dc.date.issued2016-03-04-
dc.identifier.citationGONÇALVES, Ana Cristina Resende. Ccomplexos de PdII, PtII e AuIII com tiossemicarbazonas derivadas da diacetilmonooxima: síntese, caracterização, atividade antitrypanozoma cruzi e citotoxidade. 2016. 165f. Dissertação (Mestrado em Química) - Programa de Pós-Graduação Multicêntrico em Química de Minas Gerais, Universidade Federal do Triângulo Mineiro, Uberaba, 2016.por
dc.description.resumoA doença de Chagas afeta aproximadamente 8 milhões de pessoas em todo o mundo. Infelizmente, o tratamento desta enfermidade é restrito a dois fármacos, os compostos nitroheterocíclicos benzonidazol e nifurtimox, os quais geram efeitos colaterais severos, além de serem ineficazes na fase crônica da doença. Neste sentido, compostos pertencentes à classe das tiossemicabazonas têm atraído a atenção de muitos pesquisadores, em função da atividade tripanocida apresentada. Por outro lado, compostos contendo o grupo oxima são amplamente usados na medicina como agentes quelantes em kits instantâneos para preparação de radiofármacos de 99mTc. Logo, a combinação destas duas classes traz a possibilidade de obtenção de agentes quelantes que possam ser utilizados na complexação de metais de transição e, assim, dar origem a novos potenciais fármacos para atuar em múltiplos alvos do Trypanosoma cruzi, parasita causador da doença de Chagas. Baseado neste fato, este trabalho teve como principal objetivo realizar a síntese e caracterização de novos complexos de PtII, PdII e AuIII com um ligante tiossemicarbazona derivado da diacetilmonooxima e também variar os ligantes na quarta posição de coordenação. No total foram sintetizados dez complexos utilizando-se a diacetilmonooxima-etil-tiossemicarbazona (H2L1) como ligante, os quais foram divididos ao longo do texto em três classes de compostos com características inerentes: (i) Complexos halogenados: [MX(HL1)] (M = PtII, PdII, X = Cl ou I) e [MX(L1)] (M = AuIII, X = Cl); (ii) Complexos com o ligante trifenilfosfano: [M(L1)(PPh3)] (M = PtII, PdII); (iii) Complexos Polinucleares de PtII. Os rendimentos das reações para obtenção dos complexos com ligantes clorido, iodido, trifenilfosfano e dos complexos polinucleares foram em torno de 60%, 80%, 50% e 50%, respectivamente. A elucidação estrutural e as propriedades dos compostos foram determinadas com base nas seguintes técnicas: análise elementar (CHNS), ponto de fusão, condutimetria, espectroscopias de absorção na região do infravermelho e UV-Vis, RMN (1H e 31P), espectrometria de massas e difração de raios X em monocristal. Após a caracterização, a atividade tripanocida e a citotoxicidade in vitro para o H2L1 e para os compostos mononucleares obtidos foram determinadas. A atividade tripanocida do ligante livre H2L1 e dos seus derivados foi avaliada contra a cepa CL Brener do T. cruzi, os quais apresentaram concentração citotóxica (CC50try) na faixa de 2,37 µM a 104,8 µM. Além disso, para o cálculo do índice de seletividade (IS), a citotoxicidade doscompostos também foi determinada frente à células normais da linhagem celular LLC-MK2, apresentando concentração citotóxica (CC50) com valores que variaram de 1,9 µM à 500 µM. Os resultados obtidos mostraram que a complexação do ligante tiossemicarbazona H2L1 aos centros metálicos de PtII, PdII e AuIII potencializa a atividade tripanocida in vitro e que a citotoxicidade contra células normais é dependente tanto do centro metálico quanto dos seus coligantes. Dentro da série estudada, o complexo de AuIII demonstrou o maior potencial, apresentando um IS acima de 87,9 e, portanto, sendo indicado para mais estudos biológicos e como forte candidato para ser utilizado como um agente para o tratamento da doença de Chagas.por
dc.description.abstractChagas disease affects approximately 8 million people worldwide. Unfortunately, the treatment of this disease is limited to two drugs, the nitroheterocyclics compounds benznidazole and nifurtimox, which lead to severe side effects, besides being inefficient in the chronic phase of the disease. In this sense, compounds belonging to the class of the thiosemicabazones have attracted the attention of many researchers due to the known trypanocidal activity of such compounds. On the other hand, oxime containing compounds are commonly used in the medicine as chelating agents in instant kits for preparation of 99mTc radiopharmaceuticals. Therefore, the combination of both classes seems to be suitable for the acquirement of chelating agents which could be used in the complexation of transition metals and then give origin to new drugs with potential to affect multiple targets of the Trypanosoma cruzi, parasite responsible for Chagas disease. Based on this fact, the main objective of this work was to explore the synthesis and characterization of new PtII, PdII and AuIII complexes containing a thiosemicarbazone ligand derived from diacetylmonooxime (H2L) and also to change the ligands at the fourth coordination site. In total, ten complexes were synthesized starting from the diacetylmonooxime-ethyl-thiosemicarbazone (H2L1) ligand, which are divided in the text into three classes of compounds with inherent characteristics: (i) Halogen containing complexes: [MX(HL1)] (M = PtII or PdII, X = Cl– or I–) and [MX(L1)] (M = AuIII, X = Cl); (ii) Triphenylphosphane containing complexes: [M(L1)(PPh3)] (M = PtII, PdII); (iii) PtII polinuclear complexes. The yields of the reactions to prepare the complexes containing the chlorido, iodido, triphenylphosphano ligands and the polynuclear complexes were around 60%, 80%, 50% and 50%, respectively. The structural elucidation and properties of the compounds were determined with basis on the following techniques: elemental analysis (CHNS), melting point determination, conductometry, UV-Vis and FTIR spectroscopies, NMR (1H and 31P), mass spectrometry and X-ray diffraction on single crystal. After the complete characterization, the in vitro trypanocidal activity and the cytotoxicity of H2L1 and of the mononuclear compounds were evaluated. The trypanocidal activity of the free ligand (H2L1) and its derivatives was assessed against CL Brener strains of T. cruzi, which showed cytotoxic concentration (CC50try) in the range of 2.37 µM to 104.8 µM. Moreover, in order to calculate the selectivity index (SI), the cytotoxicity of the compounds was also determinedagainst the normal cells of the LLC-MK2 cell line, showing cytotoxic concentration (CC50) with values ranging from 1.9 µM to 500 μM. The results revealed that the complexation of the thiosemicarbazone ligand H2L1 to the metal centers PtII, PdII and AuIII increases the in vitro trypanocidal activity and that the cytotoxicity against normal cells is dependent on the metal center as well as on the ancillary ligands. Within the studied series, the AuIII complex showed the greater potential, with a SI higher than 87.9, consequently, being indicated for further biological studies and as a strong candidate to be used as a Chagas’ disease treatment agent.eng
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológicopor
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superiorpor
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Geraispor
dc.formatapplication/pdf*
dc.thumbnail.urlhttp://bdtd.uftm.edu.br/retrieve/3235/Dissert%20Ana%20C%20R%20Goncalves.pdf.jpg*
dc.languageporpor
dc.publisherUniversidade Federal do Triângulo Mineiropor
dc.publisher.departmentInstituto de Ciências Exatas, Naturais e Educação - ICENEpor
dc.publisher.countryBrasilpor
dc.publisher.initialsUFTMpor
dc.publisher.programPrograma de Pós-Graduação Multicêntrico em Química de Minas Geraispor
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dc.rightsAcesso Abertopor
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectTiossemicarbazonas.por
dc.subjectComplexos metálicos.por
dc.subjectComplexos polinucleares.por
dc.subjectAtividade tripanocida.por
dc.subjectCitotoxicidade.por
dc.subjectDoença de Chagas.por
dc.subjectThiosemicarbazones.eng
dc.subjectMetal complexes.eng
dc.subjectTrypanocidal activity.eng
dc.subjectCytotoxicity.eng
dc.subjectChagas’ disease.eng
dc.subject.cnpqQuímicapor
dc.titleCcomplexos de PdII, PtII e AuIII com tiossemicarbazonas derivadas da diacetilmonooxima: síntese, caracterização, atividade antitrypanozoma cruzi e citotoxidadepor
dc.typeDissertaçãopor
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