Mechanism of Metal Complexes in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a kind of neurodegenerative diseases characterized by beta-amyloid deposition and neurofibrillary tangles and is also the main cause of dementia. According to statistics, the incidence of AD is constantly increasing, bringing a great burden to individuals and society. Nonetheless, there is no cure for AD, and the available drugs are very limited apart from cholinesterase inhibitors and N-Methyl-D-aspartic acid (NMDA) antagonists, which merely alleviate symptoms without delaying the progression of the disease. Therefore, there is an urgent need to develop a medicine that can delay the progression of AD or cure it. In recent years, increasing evidence suggests that metal complexes have the enormous potential to treat AD through inhibiting the aggregation and cytotoxicity of Aβ, interfering with the congregation and hyperphosphorylation of tau, regulating dysfunctional synaptic and unbalanced neurotransmitters, etc. In this review, we summarize the current metal complexes and their mechanisms of action for treating AD, including ruthenium, platinum, zinc, vanadium, copper, magnesium, and other complexes.

Keywords: Alzheimer’s disease; mechanism; metal complexes; therapeutics.

Figure 1

Major mechanisms of action of metal complexes in AD.

Figure 2

The pathogenesis of Alzheimer’s disease.

Figure 3

The chemical structures of ruthenium complexes. (A) fac-[Ru(CO)₃Cl₂(N¹-thz)]; (B) [Ru(phen)₂(bxbg)]²⁺; (C) RuApy (cis-[Ru(phen)₂(3,4Apy)₂]²⁺); (D) [Ru(p-cymene)Cl(L-1)][PF₆] and [Ru(p-cymene)Cl(L-2)][PF₆]; (E) Ru-WJ and Ru-YH; (F) NAMI-A, KP1019, PMRU20; (G) Oc(oxazolyl-based Ru(III) complexes); (H) [Ru(bpy)₂(EtPy)₂]²⁺; (I) BODIPY-ruthenium conjugates; (J) [Ru(dmbpy)(dcbpy)dppz)]; (K) Ru-1 and Ru-2 (Ru(II) complex scaffold with curcumin molecules); (L) Aromatic Ru(II) derivatives of curcumin.

Figure 3

The chemical structures of ruthenium complexes. (A) fac-[Ru(CO)₃Cl₂(N¹-thz)]; (B) [Ru(phen)₂(bxbg)]²⁺; (C) RuApy (cis-[Ru(phen)₂(3,4Apy)₂]²⁺); (D) [Ru(p-cymene)Cl(L-1)][PF₆] and [Ru(p-cymene)Cl(L-2)][PF₆]; (E) Ru-WJ and Ru-YH; (F) NAMI-A, KP1019, PMRU20; (G) Oc(oxazolyl-based Ru(III) complexes); (H) [Ru(bpy)₂(EtPy)₂]²⁺; (I) BODIPY-ruthenium conjugates; (J) [Ru(dmbpy)(dcbpy)dppz)]; (K) Ru-1 and Ru-2 (Ru(II) complex scaffold with curcumin molecules); (L) Aromatic Ru(II) derivatives of curcumin.

Figure 4

The chemical structures of platinum complexes. (A) Pt(1,10-phenanthroline)Cl₂, Pt(4,7-diphenyl-1,10-phenanthroline)Cl₂, Pt(4,7-diphenyl-1,10-phenanthroline disulfonate)Cl₂; (B) platinum phenanthrol complexes(PtCl₂(phen)); (C) Pt(II) and Pt(IV) complexes with 8-(1H-benzoimidazol-2-yl)-quinoline (8-BQ) as ligand; (D) pentacoordinate platinum(II) complexes 1Pt and 1Pt_dep.

Figure 5

The chemical structures of platinum complexes. (A) [Pt($\varphi$-MePy)(DMSO)Cl; (B) Pt(DMSO)₂Cl₂; (C) Pt(bpy)Cl₂; (D) Pt(Phen)Cl₂; (E) Pt($\varphi$-Phen)Cl₂; (F) platinum(II) complexes with different cinnamic acids.

Figure 6

The chemical structures of ZnII[btsc]. (A) ZnII(atsm); (B) ZnII(atse); (C) ZnII(atsp); (D) ZnII(atse).

Figure 7

The chemical structures of vanadium complexes. (A) BEOV; (B) [VO(dipic)(H₂O)₂]·2H₂O; (C) [VOO(dipic)](2-phepyH)·(H₂O); (D) VAC.

Figure 8

The chemical structures of copper complexes. (A) CuII[ATSM]; (B) CuII[GTSM]; (C) CuL5.

Figure 9

The chemical structure of MgT.

Figure 10

The chemical structures of other complexes. (A) NNN-L1, NNN-L2, NNN-L3; (B) IR-Me, IR-H, IR-F.