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 Aβ(25-35) Amyloid Peptide

Ist Teil von

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

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2009

Quelle

Wiley Online Library

Beschreibungen/Notizen

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