title: A gallium(III) Schiff base-curcumin complex that binds to amyloid-β plaques.
abstract: Gallium-68 is a positron-emitting isotope that can be used in positron-emission tomography imaging agents. Alzheimer's disease is associated with the formation of plaques in the brain primarily comprised of aggregates of a 42 amino acid protein called amyloid-β. With the goal of synthesising charge neutral, low molecular weight, lipophilic gallium complexes with the potential to cross the blood-brain barrier and bind to Aβ plaques we have used an ancillary tetradentate N2O2Schiff base ligand and the β-diketone curcumin as a bidentate ligand to give a six-coordinate Ga3+complex. The tetradentate Schiff base ligand adopts the cis-β configuration with deprotonated curcumin acting as a bidentate ligand. The complex binds to amyloid-β plaques in human brain tissue and it is possible that extension of this chemistry to positron-emitting gallium-68 could provide useful imaging agents for Alzheimer's disease.
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010, Victoria, Australia.
authors.forename: Jaclyn L
authors.initials: JL
authors.lastname: Lange
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010, Victoria, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hayne
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Roselt
authors.affiliation: Department of Anatomical Pathology, The Alfred Hospital, Victoria 3181, Australia.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010, Victoria, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: White
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010, Victoria, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Donnelly
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000648:ultrastructure; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism; D018360:Crystallography, X-Ray; D003474:Curcumin / Q000031:analogs & derivatives*; D005708:Gallium / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D058225:Plaque, Amyloid / Q000378:metabolism / Q000648:ultrastructure*; D012545:Schiff Bases / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D056831:Coordination Complexes; D012545:Schiff Bases; D005708:Gallium; D003474:Curcumin
keywords: Alzheimer's disease; Amyloid-beta; Diagnostic imaging; Gallium radiopharmaceuticals; Gallium(III) complexes; Positron-emission tomography