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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

Complexos de metais de transição multifuncionais para o tratamento e diagnóstico da doença de Alzheimer / Multifunctional transition metal complexes to treatment and diagnosis of Alzheimer´s disease

Silva, Débora Eduarda Soares 29 February 2016 (has links)
Submitted by Regina Correa (rehecorrea@gmail.com) on 2016-09-19T20:45:09Z No. of bitstreams: 1 DissDESS.pdf: 3515899 bytes, checksum: 79693b6b1e1d324fada28f6444eec538 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2016-09-23T14:08:22Z (GMT) No. of bitstreams: 1 DissDESS.pdf: 3515899 bytes, checksum: 79693b6b1e1d324fada28f6444eec538 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2016-09-23T14:08:54Z (GMT) No. of bitstreams: 1 DissDESS.pdf: 3515899 bytes, checksum: 79693b6b1e1d324fada28f6444eec538 (MD5) / Made available in DSpace on 2016-09-23T14:19:14Z (GMT). No. of bitstreams: 1 DissDESS.pdf: 3515899 bytes, checksum: 79693b6b1e1d324fada28f6444eec538 (MD5) Previous issue date: 2016-02-29 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / This work describes the synthesis and characterization of complexes cis-[Ru (phen)2(L)2]2+, where phen = 1,10-phenanthroline; L = 3,4-diaminopyridine and 4-aminopyridine, as well results for in vitro AD diagnosis and treatment. The complexes are soluble and stable in aqueous solution, display absorption (max = 480 nm;  = 9500 mol-1 L cm-1) and emission (em = 650 nm;  = 129 ns, 1.3 ns) in the region visible, and Stokes shift about 5000 cm-1. The luminescence of the complexes was incorporated into the cytoplasm of Neuro 2a cells, and showed no apparent damage of cell membrane integrity, morphology, and cytoxicity (IC50 >> 50 M). The inhibitory activity of complexes was evaluated for human recombinant acetylcholinesterase (hAChE) and butyrylcholinesterase from human serum (hBuChE) using the spectrophotometric method proposed by Ellman. The complexes are 4-fold more potent to hAChE than hBuChE, and the Lineweaver-Burk analysis indicated a reversible and mixed-type inhibition for both complexes. The antioxidant capacity of complexes was evaluated from the analysis of hydroxyl radical scavenging, and using the stable radicals 2,2- diphenil-1-picrylhydrazyl (DPPH•) and the 2,2-azinobis-3ethylbenzothiazoline- 6-sulphonate (ABTS•+). The complex cis-[Ru(phen)2(3,4-Apy)2]2+ showed a great antioxidant ability against the tested radicals. We used the luminescence of complexes to monitor in real time the self-aggregation of A with the FLIM technique. Under the same experimental conditions, the complexes bind to A1- 40 and to central hydrophobic core A15-21, but not to A22-35, that lacks the apolar Val18 and Phe20 residues, this indicates that the complexes can recognize and align specific sites of the A peptide. / Este trabalho descreve a síntese e caracterização dos complexos cis- [Ru(phen)2(L)2]2+, em que phen = 1,10-fenantrolina; L= 3,4-diaminopiridina e 4- aminopiridina, assim como resultados in vitro para o diagnóstico e tratamento da DA. Os complexos são estáveis e solúveis em solução aquosa, absorvem (máx = 480 nm,  = 9500 mol-1 L cm-1) e emitem ( em = 650 nm,  = 129 ns; 1,3 ns) na região do visível, e apresentam deslocamento de Stokes na ordem de 5000 cm-1. A luminescência dos complexos foi incorporada no citoplasma de células Neuro 2a, e não apresentaram danos aparentes a integridade da membrana celular, a morfologia e citotoxicidade (IC50 >> 50 M). A atividade inibitória dos complexos foi avaliada para as enzimas acetilcolinesterase recombinante humana (hAChE) e butirilcolinesterase de soro humano (BuChE) empregando o método espectrofotométrico proposto por Ellman. Os complexos são quatro vezes mais potentes na inibição da enzima AChE do que da BuChE, e a análise de Lineweaver-Burk indicou uma inibição reversível e do tipo mista para os dois complexos. A capacidade antioxidante dos complexos foi investigada a partir da análise do sequestro do radical hidroxila, e também empregando os modelos de radicais estáveis DPPH• (2,2-difenil-1picril-hidrazila) e ABTS•+ (2,2'-azinobis- [3-ethylbenzthiazoline-6-sulfonic acid]). O complexo cis-[Ru(phen)2(3,4- Apy)2]2+ apresentou boa habilidade antioxidante frente aos radicais testados. A luminescência dos complexos foi utilizada para monitorar em tempo real a agregação do A1-40 com o uso da técnica FLIM. Sob as mesmas condições experimentais, os complexos se ligam ao A1-40 e ao centro hidrofóbico A15-21, mas não ao A22-35, no qual os resíduos apolares Val18 e Phe20 estão ausentes, o que indica que os complexos podem reconhecer e alinhar locais específicos do peptídeo A. / Processo n° 2014/07935-8

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