Pt(II) versus Pt(IV) in Carbene Glycoconjugate Antitumor Agents: Minimal Structural Variations and Great Performance Changes

Abstract

Octahedral Pt(IV) complexes ( 2Pt–R ) containing a glycoconjugate carbene ligand were prepared and fully characterized. These complexes are structural analogues to the trigonal bipyramidal Pt(II) species ( 1Pt–R ) recently described. Thus, an unprecedented direct comparison between the biological properties of Pt compounds with different oxidation states and almost indistinguishable structural features was performed. The stability profile of the novel Pt(IV) compounds in reference solvents was determined and compared to that of the analogous Pt(II) complexes. The uptake and antiproliferative activities of 2Pt–R and 1Pt–R were evaluated on the same panel of cell lines. DNA and protein binding properties were assessed using human serum albumin, the model protein hen egg white lysozyme, and double stranded DNA model systems by a variety of experimental techniques, including UV–vis absorption spectroscopy, fluorescence, circular dichroism, and electrospray ionization mass spectrometry. Although the compounds present similar structures, their in-solution stability, cellular uptake, and DNA binding properties are diverse. These differences may represent the basis of their different cytotoxicity and biological activity.

Thiosemicarbazone Derivatives as Inhibitors of Amyloid-β Aggregation: Effect of Metal Coordination

“…It has been shown that the electronic spectra of metal complexes can be modulated by their interaction with proteins; for instance, a hyperchromic effect can be observed . Hence, potential changes of the UV–vis absorption properties of 1 – 3 upon interaction with lysozyme have been investigated.…”

“…It has been shown that the electronic spectra of metal complexes can be modulated by their interaction with proteins; for instance, a hyperchromic effect can be observed. 42 Hence, potential changes of the UV−vis absorption properties of 1−3 upon interaction with lysozyme have been investigated. UV− vis spectra of 1−3 have therefore been recorded with and without the presence of lysozyme for 24 h. The corresponding comparative data (absorption values at λ = 433 nm) are depicted in Figure 4.…”

Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

“…For uptake experiments, 1 × 10 6 cells of both immortalized and cancer cells were plated and treated with AP-1-encapsulated AFt at the concentration equal to IC50 (AP-1 concentration = 10.91 µM) for 48 h. At the end of incubation, cells were treated as described in Annunziata et al [52]. Each cellular pellet was transferred in a PE vial and digested in a thermo-reactor at 80 °C for 8 h with 2 mL of aqua regia (HCl supra-pure grade and HNO3 supra-pure grade in a 3:1 ratio).…”

Square-Planar vs. Trigonal Bipyramidal Geometry in Pt(II) Complexes Containing Triazole-Based Glucose Ligands as Potential Anticancer Agents

“…Among these, sugars are an excellent example due to their biocompatibility, the possibility of modulating their chemico-physical properties, and the ability of selective recognition by cancer cells, known as the Warburg effect [19][20][21][22][23][24][25][26][27][28]. In this context, over the last few years, our research group has proposed new organometallic glycoconjugate platinum complexes as innovative anticancer agents [29][30][31][32][33].…”