Development of a Platinum Complex as an anti‐Amyloid Agent for the Therapy of Alzheimer’s Disease

Abstract

Brainwash! A platinum complex (see scheme) was developed that could be administered orally and reduce the amyloid burden in the brains of transgenic mouse models suffering from Alzheimer's disease. Analyses of brain tissues showed that treatment with the Pt compound led to a 26 % decrease in the number of amyloid β‐peptide plaques.

Tools of the Trade: Investigations into Design Strategies of Small Molecules to Target Components in Alzheimer's Disease

“…17 The use of metal complexes, however, still needs to be subjected to more intensive in vivo testing, especially because of the potential toxicity associated with the introduction of exogenous redox‐active metals into an environment already affected by oxidative stress. In the case of Pt complexes, Pt II is most likely redox‐inactive within the cell; however, its toxicity in biological systems presents additional challenges 10g–h. The use of Pt IV complexes that can then be reduced by natural reductants (e.g., glutathione) back to labile Pt II upon entering the cell might offer one solution to this obstacle 10g–h…”

“…In the case of Pt complexes, Pt II is most likely redox‐inactive within the cell; however, its toxicity in biological systems presents additional challenges 10g–h. The use of Pt IV complexes that can then be reduced by natural reductants (e.g., glutathione) back to labile Pt II upon entering the cell might offer one solution to this obstacle 10g–h…”

Ruthenium(II) polypyridyl complexes with hydrophobic ancillary ligand as Aβ aggregation inhibitors

“…Further phenanthroline interacts with aromatic residues of Aβ by π-π interactions. For the cis-platin, a completely different mode of binding takes place which involves covalent binding of Pt(II) with sulphur of Met residue of Aβ [12,13,24]. Although the adducts are formed by platination of Aβ, cis-platin exhibits no potential against Aβ aggregation indicating the crucial role of non-covalent π-π interaction in L-PtCl 2 Aβ binding.…”

“…However recent pioneering work of Barnham and co-workers on platinum complexes as potential Aβ aggregation inhibitors opened up a new class of metal based anti-Aβ aggregation compounds [12]. A range of phenanthroline Pt(II) complexes (L-PtCl 2 ) (where, L is phenanthroline based ligand) were found to interact with Aβ peptide and inhibit its neurotoxicity [12,13]. Inspired by these promising results, other similar type of metal complexes such as cyclometallated platinum complexes [14], platinum chelates [15], benzimidazole Ir, Ru and Pt complexes [16], Ir and Rh complexes containing planar aromatic C-N coligand [17], binuclear Ru(II)-Pt(II) complexes [18] have been developed to reduce Aβ neurotoxicity.…”

Cognitive Enhancers (Nootropics). Part 3: Drugs Interacting with Targets other than Receptors or Enzymes. Disease-Modifying Drugs. Update 2014

“…A Tetrachloro-Platinum complex on a 8-(1Hbenzoimidazol-2-yl)-quinoline (8-BQ) scaffold was shown to reduce the number of A␤ plaques by 29% after an oral treatment for 18 weeks of Tg2576 mice with a daily dose of 15 mg/kg [531]. For a review, see [532].…”