title: 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.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Salerno, 84084 Fisciano, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Mario
authors.initials: M
authors.lastname: Scrima
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Cioffi
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.forename: Marina
authors.initials: M
authors.lastname: Sala
authors.forename: Claudio
authors.initials: C
authors.lastname: Aquino
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002942:Circular Dichroism; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013844:Thiazoles; C074636:amyloid beta-protein (25-35)