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Proflavine derivatives as fluorescent imaging agents of amyloid deposits
Authors:Garin Dominique  Oukhatar Fatima  Mahon Andrew B  Try Andrew C  Dubois-Dauphin Michel  Laferla Frank M  Demeunynck Martine  Sallanon Marcelle Moulin  Chierici Sabine
Institution:a INSERM, Unit U877, J Fourier University, La Tronche, France
b Département de Chimie Moléculaire, UMR-5250 & ICMG FR-2607, CNRS-Université Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France
c Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia
d Department of Pathology and Immunology, CMU-University of Geneva, Geneva 4, Switzerland
e Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA
Abstract:A series of proflavine derivatives for use to further image Aβ amyloid deposits were synthesized and characterized. Aged 3xTg-AD (23 months old) mice hippocampus sections incubated with these derivatives revealed preferential labeling of amyloid plaques. Furthermore an in vitro binding study showed an inhibitory effect, although moderate, of these compounds on Aβ40 fibril formation. This study highlights the potential of proflavine as a molecular scaffold for designing new Aβ imaging agents, its native fluorescence allowing in vitro neuropathological staining in AD damaged brain sections.
Keywords:Proflavine  Click chemistry  Fluorescent markers  Amyloid deposits imaging
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