A Comparative Study of the Effects of Platinum (II) Complexes on β-Amyloid Aggregation: Potential Neurodrug Applications

Abstract

Herein the effects of three platinum complexes, namely (SP-4-2)-(2,2′-bipyridine)dichloridoplatinum(II), Pt-bpy, (SP-4-2)-dichlorido(1,10-phenanthroline) platinum(II), Pt-phen, and (SP-4-2)-chlorido(2,2′:6′,2′′-terpyridine)platinum(II) chloride, Pt-terpy, on the aggregation of an amyloid model system derived from the C-terminal domain of Aβ peptide (Aβ21–40) were investigated. Thioflavin T (ThT) binding assays revealed the ability of Pt(II) compounds to repress amyloid aggregation in a dose-dependent way, whereas the ability of Aβ21–40 peptide to interfere with ligand field of metal complexes was analyzed through UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. Spectroscopic data provided micromolar EC50 values and allowed to assess that the observed inhibition of amyloid aggregation is due to the formation of adducts between Aβ21–40 peptide and complexes upon the release of labile ligands as chloride and that they can explore different modes of coordination toward Aβ21–40 with respect to the entire Aβ1–40 polypeptide. In addition, conformational studies through circular dichroism (CD) spectroscopy suggested that Pt-terpy induces soluble β-structures of monomeric Aβ21–40, thus limiting self-recognition. Noticeably, Pt-terpy demonstrated the ability to reduce the cytotoxicity of amyloid peptide in human SH-SY5Y neuroblastoma cells. Presented data corroborate the hypothesis to enlarge the application field of already known metal-based agents to neurodegenerative diseases, as potential neurodrugs.

Glucosyl Platinum(II) Complexes Inhibit Aggregation of the C-Terminal Region of the Aβ Peptide

“…Similarly, the b series signals were encountered also in the spectra of Aβ 21–40 adducts. The doubly charged signals at m / z 1001.95, 1010.59, and 1133.03 (Figure B) are in accordance with the b 19 signal of Aβ 21–40 bound to naked Pt­(II), Pt + Me, and Pt + sugar + Me fragments, as previously reported …”

“…Very recently, we have investigated the ability of a series of square-planar Pt­(II) complexes to inhibit the aggregation of amyloid peptides. − Among the investigated systems, the pyridine-based platinum­(II) complex, called Pt-terpy, exhibited good inhibitory effects of amyloid aggregation, also allowing, for its better water solubility when compared to other investigated complexes, to get insights into the mechanism of action of these types of molecules: the presence of the Pt complex stabilized soluble β-structures of the Aβ 21–40 peptide . Some of us also designed new pentacoordinate glycoconjugate platinum­(II) complexes that can act as anticancer compounds .…”

Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer

“…Washes were made with 1% acetic acid until the removal of the unbound dye and the plates were left to dry. The dye was solubilized in TRIS-HCl 10 mM as previously described [ 23 , 24 ]. The reading was performed at 495 nm by Glomax ® Discover Microplate Reader (Promega, Madison, WI, USA).…”

Microwave-Assisted Synthesis: Can Transition Metal Complexes Take Advantage of This “Green” Method?

“…Other Pt(II) complexes containing several pyridines were synthesized starting from [PtCl 4 ] 2− or [PtCl 2 (cod)] even though not all the procedures overcome the traditional methods [178]. Starting from those results, [PtCl 4 ] 2− also reacted with phen under MW irradiation (EtOH/water, 60 • C, 5 + 15 min, 10 W) in 51% yield [179].…”