Cisplatin Inhibits the Formation of a Reactive Intermediate during Copper-Catalyzed Oxidation of Amyloid β Peptide

Cisplatin was studied for its effect on the copper-catalyzed oxidation of amyloid β (Aβ) peptide. The interaction of cisplatin with Aβ1-16 in the presence of Cu^II was investigated using cyclic voltammetry and mass spectrometry. The positive shift in the <i>E</i>_1/2 value of Aβ1-16-Cu^II suggests that the interaction of cisplatin alters the copper-binding properties of Aβ1-16. The mass spectrometry data show complete inhibition of copper-catalyzed decarboxylation/deamination of the Asp1 residue of Aβ1-16, while there is a significant decrease in copper-catalyzed oxidation of Aβ1-16 in the presence of cisplatin. Overall, our results provide a novel mode by which cisplatin inhibits copper-catalyzed oxidation of Aβ. These findings may lead to the design of better platinum complexes to treat oxidative stress in Alzheimer’s disease and other related neurological disorders

Acetylcholinesterase and Aβ Aggregation Inhibition by Heterometallic Ruthenium(II)–Platinum(II) Polypyridyl Complexes

Two heteronuclear ruthenium­(II)–platinum­(II) complexes [Ru­(bpy)₂(BPIMBp)­PtCl₂]²⁺ (<b>3</b>) and [Ru­(phen)₂(BPIMBp)­PtCl₂]²⁺ (<b>4</b>), where bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, and BPIMBp = 1,4′-bis­[(2-pyridin-2-yl)-1H-imidazol-1-ylmethyl]-1,1′-biphenyl, have been designed and synthesized from their mononuclear precursors [Ru­(bpy)₂(BPIMBp)]²⁺ (<b>1)</b> and [Ru­(phen)₂(BPIMBp)]²⁺ (<b>2</b>) as multitarget molecules for Alzheimer’s disease (AD). The inclusion of the cis-PtCl₂ moiety facilitates the covalent interaction of Ru­(II) polypyridyl complexes with amyloid β (Aβ) peptide. These multifunctional complexes act as inhibitors of acetylcholinesterase (AChE), Aβ aggregation, and Cu-induced oxidative stress and protect neuronal cells against Aβ-toxicity. The study highlights the design of metal based anti-Alzheimer’s disease (AD) systems