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000775423.pdf: 5973935 bytes, checksum: 4c211bb2075b58e6ac765675802ecb19 (MD5) / Ligantes N,S-doadores, bem como as fenantrolinas, vêm sendo amplamente utilizados na obtenção de complexos de elevada citotoxicidade. Tendo em vista estas propriedades, esses ligantes foram utilizados na síntese de complexos de paládio(II) com a finalidade de obter compostos com atividade antitumoral. A escolha do metal foi baseada na similaridade entre sua química de coordenação e a da platina(II), cujos complexos, como a cisplatina e a carboplatina, são amplamente utilizados como agentes quimioterápicos. Este trabalho apresenta a síntese de 4 ligantes e 23 complexos de Pd(II), dos quais 18 são inéditos. Os complexos 1-4 apresentam fórmula geral [PdX2(tmdmPz)] {X = Cl, Br, I, SCN; tmdmPz = 3,5-dimetil-1-metiltiocarbamoilpirazol}. Os complexos 5-23 são do tipo [PdCl2(NN)] ou [Pd(NN)(L)2]Cl2 {NN = 1,10-fenantrolina (phen), 4,7-dicloro-1,10-fenantrolina (Cl2-phen), dipirido[3,2-a:2’3’-c]fenazina (dppz), 7-metildipirido[3,2-a:2’3’-c]fenazina (CH3-dppz), 7-clorodipirido[3,2-a:2’3’-c]fenazina (Cl-dppz); L = tioureia (tu), N-metiltioureia (mtu), N,N’-dimetiltioureia (dmtu), N-feniltioureia (ftu)}. A caracterização dos compostos foi feita por espectroscopia na região do IV, RMN de 1H e 13C, análise elementar e condutividade. Os complexos preparados tiveram sua citotoxicidade avaliada frente a células tumorais e alguns ensaios foram realizados com o objetivo de avaliar sua possível interação com o DNA e, posteriormente, estabelecer relações estrutura-atividade. Para cada grupo de compostos, testes pertinentes foram realizados. Destacam-se os seguintes experimentos: reação com a guanosina, desenrolamento do DNA, determinação do Kb por espectroscopia UV, deslocamento do brometo de etídio, desnaturação térmica do DNA e coeficiente de partição dos complexos. Os resultados obtidos indicaram que diversos fatores interferem tanto na citotoxicidade quanto na afinidade pelo DNA. Dentre as propriedades mais... / The use of N,S-donor ligands, as well as phenanthrolines, has been widely explored in the preparation of complexes with increased cytotoxicity. Thus, these ligands were employed in the synthesis of new palladium(II) complexes with the aim to obtain compounds displaying good antitumor activity. The choice for using this metal was based on the similarity of its coordination chemistry to that of platinum(II) whose compounds, such as cisplatin and carboplatin, are widely used as antitumor agents. This works presents the synthesis of 4 ligands and 23 Pd(II) complexes. Complexes 1-4 have the general formulae [PdX2(tmdmPz)] {X = Cl, Br, I, SCN; tmdmPz = 3,5-dimethyl-1-methylthiocarbamoylpyrazole}. Complexes 5-23 of the type [PdCl2(NN)] or [Pd(NN)(L)2]Cl2 {NN = 1,10-phenanthroline (phen), 4,7-dichloro-1,10-phenanthroline (Cl2-phen), dipyrido[3,2-a:2’3’-c]phenazine (dppz), 7-methyldipyrido[3,2-a:2’3’-c]phenazine (CH3-dppz), 7-chlorodipyrido[3,2-a:2’3’-c]phenazine (Cl-dppz); L = thiourea (tu), N-methylthiourea (mtu), N,N’-dimethylthiourea (dmtu), N-phenilthiourea (ftu)} have been synthesized. These complexes were characterized by IR spectroscopy, 1H and 13C NMR, elemental analysis and molar conductivity. The complexes were tested against tumor cell lines. Some studies have been made aiming at evaluating their possible interaction with DNA and to establish preliminary structure-activity relationships. For each group of compounds selected experiments were made, including: reaction with guanosine, DNA unwinding, Kb determination, bromide ethidium displacement, thermal denaturation of DNA and partition coefficient of the complexes. The results indicated that cytotoxicity and also DNA binding affinity are influenced by several factors such as electronic distribution, hydrophobic effects and stereochemistry.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unesp.br:11449/110712 |
| Date | 24 February 2014 |
| Creators | Rocha, Carolina Valério Barra [UNESP] |
| Contributors | Universidade Estadual Paulista (UNESP), Netto, Adelino Vieira de Godoy [UNESP], Frem, Regina Célia Galvão [UNESP] |
| Publisher | Universidade Estadual Paulista (UNESP) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Unknown |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | 165 f. : il. |
| Source | Aleph, reponame:Repositório Institucional da UNESP, instname:Universidade Estadual Paulista, instacron:UNESP |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | -1, -1, -1 |
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