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

Fluorescent Copper Probe Inhibiting Aβ1–16-Copper(II)-Catalyzed Intracellular Reactive Oxygen Species Production

A variety of fluorescent probes are proposed to monitor the intracellular copper content. So far, none of the probes have been evaluated for their potential to inhibit copper-associated intracellular oxidative stress. Herein, we studied the ability of a fluorescent copper probe, OBEP-CS1, to inhibit intracellular oxidative stress associated with an amyloid β (Aβ) peptide–copper complex. The data showed that OBEP-CS1 completely inhibits the copper-catalyzed oxidation as well as decarboxylation/deamination of Aβ1–16. Moreover, the cell imaging experiments confirmed that OBEP-CS1 can inhibit Aβ-Cu^II-catalyzed reactive oxygen species production in SH-SY5Y cells. We also demonstrated that Aβ1–16 peptide can bind intracellular copper and thereby exert oxidative stress

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