Liberation of copper from amyloid plaques: making a risk factor useful for Alzheimer's disease treatment.
Alzheimer's disease (AD) is a complex multifactorial syndrome. Metal chelator and Aβ inhibitor are showing promise against AD. In this report, three small hybrid compounds (1, 2, and 3) have been designed and synthesized utilizing salicylaldehyde (SA) based Schiff bases as the chelators and benzothiazole (BT) as the recognition moiety for AD treatment. These conjugates can capture Cu(2+) from Aβ and become dimers upon Cu(2+) coordination and show high efficiency for both Cu(2+) elimination and Aβ assembly inhibition. Besides, the complexes have superoxide dismutase (SOD) activity and significant antioxidant capacity and are capable of decreasing intracellular reactive oxygen species (ROS) and increasing cell viability. All these results indicate that the multifunctional metal complexes which have Aβ specific recognition moiety and metal ion chelating elements show the potential for AD treatment. Therefore, our work will provide new insights into exploration of more potent amyloid inhibitors.
Laboratory of Chemical Biology, Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Changchun, Jilin 130022, China.
Jie
J
Geng
Meng
M
Li
Li
L
Wu
Jinsong
J
Ren
Xiaogang
X
Qu
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002733:Chlorophenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D009596:Nitrophenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism
C578482:(E)-2-((benzo(d)thiazol-2-ylimino)methyl)-4-chlorophenol; C578483:(E)-2-((benzo(d)thiazol-2-ylimino)methyl)-4-nitrophenol; C578481:(E)-2-((benzo(d)thiazol-2-ylimino)methyl)phenol; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D002614:Chelating Agents; D002733:Chlorophenols; D056831:Coordination Complexes; D009596:Nitrophenols; D010636:Phenols; D017382:Reactive Oxygen Species; D003300:Copper; D013482:Superoxide Dismutase