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Updated: Dec 22, 2025
A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Thiosemicarbazone Derivatives as Inhibitors of Amyloid-β Aggregation: Effect of Metal Coordination
Ana I Matesanz1, Ana B Caballero2,3, Carmen Lorenzo1
1Department of Inorganic Chemistry (M-07), School of Sciences, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Abstract:
Three thiosemicarbazone derivatives, namely 4-(dimethylamino)benzaldehyde 4,4-dimethylthiosemicarbazone (HL), 4-(dimethylamino)benzaldehyde thiosemicarbazone (HL), and 4-(dimethylamino)benzaldehyde 4-methylthiosemicarbazone (HL), have been synthesized and characterized. The three palladium(II) complexes 1-3 were prepared respectively from HL, HL, and HL. The crystal structures of two coordination compounds, namely Pd(L)2 (2) and Pd(L)2 (3), were obtained, which showed the expected square-planar environment for the metal centers. The ligand HL and the Pd(II) complexes 1-3, which are stable in buffered solutions containing up to 5% DMSO, exhibit remarkable inhibitory properties against the aggregation of amyloid-β, reducing the formation of fibrils. HL, HL, 2, and 3 display IC50 values (i.e., the concentrations required to reduce Aβ fibrillation by 50%) below 1 μM, lower that of the reference compound catechin (IC50 = 2.8 μM). Finally, in cellulo studies with E. coli cells revealed that the palladium(II) compounds are significantly more efficient than the free ligands in inhibiting Aβ aggregation inside bacterial inclusion bodies, thus illustrating a beneficial effect of metal coordination.
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