18432-95-6Relevant articles and documents
A comparative study of the effects of platinum (Ii) complexes on β-amyloid aggregation: Potential neurodrug applications
La Manna, Sara,Florio, Daniele,Iacobucci, Ilaria,Napolitano, Fabiana,De Benedictis, Ilaria,Malfitano, Anna Maria,Monti, Maria,Ravera, Mauro,Gabano, Elisabetta,Marasco, Daniela
, p. 1 - 13 (2021/03/18)
Herein the effects of three platinum complexes, namely (SP-4-2)-(2,2′-bipyridine)dichlorido platinum(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.
Anionic versus neutral Pt(II) complexes: The relevance of the charge for human serum albumin binding
Aiello, Iolinda,Ghedini, Mauro,Guzzi, Rita,Ionescu, Andreea,La Deda, Massimo,Ricciardi, Loredana,Rizzuti, Bruno
, (2020/02/18)
The focus of this work is pointing out the different behavior of two structurally related Pt(II) complexes, the anionic cyclometalated NBu4[(Bzq)Pt(Thio)], 1 and the neutral [(Phen)Pt(Thio)], 2, (Bzq = benzo[h]quinoline, Phen = 1,10-phenantroline, Thio = 1,2-benzenedithiolate), on the interaction with human serum albumin (HSA), a key drug-delivery protein in the bloodstream. Being very limited the number of anionic Pt(II) complexes reported to date, this is a pioneering example of report on a protein-ligand interaction involving a negatively charged platinum compound. The study was carried out by using fluorescence spectroscopy, differential scanning calorimetry and molecular docking simulations. The results revealed a strong binding affinity between the anionic compound and the protein, whereas a weak/moderate binding interaction was highlighted for the neutral one. Comparative studies with site specific ligands (warfarin and ibuprofen), allowed us to identify the protein binding sites of the two compounds. The work aims to shed light on the relevance of the charge in designing new drugs with a favorable binding affinity for HSA, which strongly contributes to influence their pharmacological and toxicological profile.
Conformational analysis and potential anticancer activity of [Pt(phen)(L1 -κ: S)2] studied by single crystal X-ray diffraction and variable temperature 1H and 195Pt NMR spectroscopy
Kangara, Edmore F.,Peega, Tebogo,Harmse, Leonie,Van Wyk, Juanita L.,Levendis, Demetrius C.,Kotzé, Izak A.
, p. 3665 - 3672 (2019/03/05)
The mixed-ligand [Pt(phen)(L1-κS)2] complex, in which two N,N-diethyl-N′-1-naphthoylthioureato ligands (L1)- coordinate in an unusual κS-thio/amido mode, crystallises in two solvatomorphs, form I and form II, whose structures have been determined by single crystal X-ray diffraction. These crystals were obtained from tetrahydrofuran and methanol/water respectively showing interesting sandwich (form I) and half-sandwich (form II) intramolecular π-stacking arrangements between the naphthoyl moiety of the acylthioureato ligands and the 1,10-phenanthroline ligand that adopt an anti-conformation above and below the square planar coordination plane. Variable temperature 1H and 195Pt NMR spectroscopy showed that these π-stacking arrangements persist in methanol solution especially at lower temperatures, where significant chemical shift shielding and asymmetry are observed indicating at least 3 conformers at -50 °C. A preliminary study indicates that this new compound may have potential as a new anticancer agent since it is active against the A549 lung cancer cell-line with an IC50 value of 6 ± 0.9 μM.