Details

Autor(en) / Beteiligte

• Campiglia, Pietro
• Scrima, Mario
• Grimaldi, Manuela
• Cioffi, Giuseppina
• Bertamino, Alessia
• Sala, Marina
• Aquino, Claudio
• Gomez-Monterrey, Isabel
• Grieco, Paolo
• Novellino, Ettore
• D'Ursi, Anna Maria

Titel

A new series of 1,3-dihidro-imidazo[1,5-c]thiazole-5,7-dione derivatives: synthesis and interaction with Abeta(25-35) amyloid peptide

Ist Teil von

• Chemical biology & drug design, 2009-09, Vol.74 (3), p.224-233

Ort / Verlag

England

Erscheinungsjahr

2009

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Deposition of senile plaques composed of fibrillar aggregates of Abeta-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 Abeta(25-35) peptide was evaluated using circular dichroism, nuclear magnetic resonance and thioflavin fluorescence spectroscopy. A molecular model for Abeta(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 Abeta(25-35) varies as a function of the overall structural features of the ligands rather contributions from specific individual substituents.