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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

[en] MN(II) AND CO(II) COMPLEXES WITH THIOSEMICARBAZONES AND FLUORQUINOLONES: SYNTHESIS, SPECTROSCOPIC AND ELECTROCHEMICAL STUDIES AND BIOLOGICAL ACTIVITY / [pt] COMPLEXOS DE MN(II) E CO(II) DE TIOSSEMICARBAZONAS E FLUORQUINOLONAS: SÍNTESES, ESTUDOS DAS PROPRIEDADES ESPECTROSCÓPICAS E ELETROQUÍMICAS E TESTES DE ATIVIDADE BIOLÓGICA

RENATA SOBRAL SILVA 15 September 2009 (has links)
[pt] Tiossemicarbazonas e fluorquinolonas são compostos que apresentam uma grande diversidade de aplicações farmacológicas. Este trabalho compreende um estudo de tiossemicarbazonas e seus complexos de Mn(II) e Co(II) com potencial ação antiparasitária e antitumoral e de complexos de Mn(II) e Co(II) de fluorquinolonas com atividade antimicrobiana. N(4)-metil tiossemicarbazonas derivadas de 4-nitrobenzaldeído (H4NO2Fo4M), 4-nitroacetofenona (H4NO2Ac4M) e 4-nitrobenzofenona (H4NO2Bz4M) e seus complexos de Mn(II) e Co(II), [Mn(H4NO2Fo4M)2Cl2], [Mn(H4NO2Ac4M)2Cl2], [Mn(H4NO2Bz4M)2Cl2], [Co(H4NO2Fo4M)2Cl2], [Co(H4NO2Ac4M)2Cl2], [Co(H4NO2Bz4M)2Cl2], foram obtidos e caracterizados. A estrutura cristalográfica de N(4)-metil 4-nitrobenzaldeído tiossemicarbazona (H4NO2Fo4M) foi determinada. Estudos eletroquímicos mostram que o radical Ar-NO2, um dos intermediários no mecanismo de ação de drogas antitripanossoma, forma-se em torno de -1,0 V nas tiossemicarbazonas livres e nos complexos de Mn(II), sugerindo potencial atividade anti-tripanossoma. A fluorescência natural observada para as N(4)-metil nitrotiossemicarbazonas e de seus complexos de Mn(II) e Co(II) pode vir a servir para identificar e monitorar a presença dessas espécies no meio biológico. A toxicidade das tiossemicarbazonas e de seus complexos de Mn(II) frente à Artemia salina foi estudada como um préscreening para sua ação antitumoral. Os valores de CL50;48h (concentração letal para 50% da população exposta à droga durante 48 horas) obtidos indicam que esses compostos têm atividade citotóxica, sugerindo que poderiam igualmente apresentar ação antitumoral. Um dos grandes problemas com antibióticos empregados na clínica é o aparecimento de resistência às drogas e assim a busca de novos fármacos ativos é de extrema relevância. Em muitos casos, mecanismos de resistência celular não reconhecem complexos metálicos, embora reconheçam os ligantes. Preparamos então complexos de Mn(II) e Co(II) de norfloxacina e esparfloxacina, [MnCl2(NOR)(H2O)2], [CoCl2(NOR)(H2O)2], [MnCl2(ESPAR)(H2O)2] e [CoCl2(ESPAR)(H2O)2], e testamos sua atividade em cepas de Staphylococcus aureus sensíveis e resistentes às drogas livres. Em resumo, acreditamos que com esse trabalho contribuímos para um melhor conhecimento da química de tiossemicarbazonas e fluorquinolonas e de suas diversas propriedades farmacológicas. / [en] Thiosemicarbazones and fluorquinolones are a class of compounds presenting a wide range of pharmacological activities. In the present work a study of thiosemicarbazones and their Mn(II) and Co(II) complexes with potential anti parasite and antitumoral activities was carried out along with an investigation of Mn(II) and Co(II) complexes of norfloxacin and sparfloxacin with antimicrobial activity. N(4)-methyl thiosemicarbazones derived from 4-nitrobenzaldehyde (H4NO2Fo4M), 4-nitroacetophenone (H4NO2Ac4M) and 4-nitrobenzophenone (H4NO2Bz4M) and their Mn(II) and Co(II) complexes, [Mn(H4NO2Fo4M)2Cl2], [Mn(H4NO2Ac4M)2Cl2], [Mn(H4NO2Bz4M)2Cl2], [Co(H4NO2Fo4M)2Cl2], [Co(H4NO2Ac4M)2Cl2], [Co(H4NO2Bz4M)2Cl2], were obtained and characterized. The crystal structure of H4NO2Fo4M has been determined. Electrochemical studies have shown that the Ar-NO2, one of the proposed intermediates in the mechanism of action of nitro-containing anti-trypanosomal drugs, is formed at approximately -1.00 V in the free thiosemicarbazones as well as in their corresponding Mn(II) complexes, suggesting their potential to act as antitrypanosomal drugs. The natural fluorescence of H4NO2Fo4M, H4NO2Ac4M, H4NO2Bz4M and Mn(II) and Co(II) complexes provides a way to identify and to monitor their concentration in biological systems. The toxicity of the thiosemicarbazones and their Mn(II) complexes against Artemia salina was assayed as a prescreening for antitumoral action. The low values of CL50;48h obtained for the studied compounds in this assay indicate that they could present antineoplastic properties. One of the major problems in the clinical treatment of infection by bacteria is the appearance of resistance and therefore the search for new drugs is extremely important. In many cases resistance mechanisms recognize the ligand but cannot recognize its metal complex. In the present work Mn(II) and Co(II) complexes of norfloxacin and sparfloxacin, [MnCl2(NOR)(H2O)2], [CoCl2(NOR)(H2O)2], [MnCl2(ESPAR)(H2O)2] and [CoCl2(ESPAR)(H2O)2] were obtained and their antibacterial activity against Staphylococcus aureus has been tested. We believe that this work contributes for a better knowledge of the chemistry of thiosemicarbazones and fluorquinolones and their pharmacological properties.

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