Complexos de metais de transição: aplicações no tratamento e diagnóstico da doença de Alzheimer
Abstract
Currently there are about 35.6 million people diagnosed with Alzheimer's
disease (AD) in the world, and it is expected that this number will double by 2050.
Causes of Alzheimer's disease are not yet known, but their symptoms are
characterized the decline of cognitive function result of overactivity of the enzyme
acetylcholinesterase (AChE); and accumulation of β-amyloid peptide (β-A) in the
brain of patients. Therefore it is important to the development of drugs that act on the
two problems of AD; cognitive decline (inhibition of AChE activity) and the
identification of fibrillar aggregates of β-A (creation of new probes). For this purpose
have been prepared and tested a series of luminescent complex; cis-[Ru(phen)2(4-
ImAC)]PF6, cis-[Ru(phen)2(4-ImAAc)]PF6, cis-[Ru(phen)2(2-Apy)](PF6)2, where phen
= 1,10-phenanthroline, ImAA = 4-imidazole acetic acid, ImAC = 4-imidazole
carboxylic acid and Apy = 2-aminopyridine. The ruthenium complexes were
synthesized, where its structural elucidation and purity were checked by NMR H1
spectroscopy and by microanalysis. The compounds are soluble in aqueous
solutions and exhibit an intense and broad absorption and emission in the visible
region. The complexes have relatively long life with 1 the order of 100 ns. The
complexes showed moderate inhibition against the enzyme AChE, with an IC50 of
about 10-20 μmol.L-1. From the images from confocal microscopy was possible to
make the location of the complex inside the cells by luminescent emission, where the
imidazole compounds were located specifically in the cytoplasmic portion of the cell,
unlike the complex with aminopyridine, which was distributed homogeneously
throughout cellular portion. It was possible to identify the formation of fibers from
measurements of emission of the luminescent complex, since these complexes have
intensity of luminescence variable with different types of Aβ aggregation. The fibrils
were also confirmed by fluorescence microscopy emission lifetime. From the results
of the complexes exhibit high pharmacological potential to the treatment of AD since
they can be used in diagnosis (identification of the fibrils) and in the treatment of AD
(AChE inhibition).
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