Deposition of senile plaques composed of fibrillar aggregates of A beta-amyloid peptide is a characteristic hallmark of Alzheimer's disease. A widely employed approach in the study of anti-Alzheimer agents involves the identification of substances able to prevent amyloid aggregation, or to disaggregate the amyloid fibrils through a direct structural interaction with the soluble or aggregated forms of the peptide. Here, we report the synthesis of a set of 1,3-dihydro-3,6-disubstituted-imidazo[1,5-c]thiazole-5,7-dione derivatives supporting different alkyl, aryl and alkylamine side chains. The ability of these compounds to interact with the A beta(25-35) peptide was evaluated using circular dichroism, nuclear magnetic resonance and thioflavin fluorescence spectroscopy. A molecular model for A beta(25-35)-ligand interactions was calculated by molecular docking procedures. Our data show that the ability of the synthesized compounds to modify the structural behaviour of A beta(25-35) varies as a function of the overall structural features of the ligands rather contributions from specific individual substituents.
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