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.
Highlights
The improvement of the anticancer performance of metalbased agents is an important task of modern chemistry.[1]
During these studies, interesting results have been obtained with a cationic complex containing a glucoconjugate carbene (1Pt−Glu in Figure 2) that showed a cytotoxic effect on cancer cells 2 orders of magnitude higher than cisplatin
We described novel five-coordinate Pt(II) compounds bearing glycoconjugate carbene ligands, which were characterized and evaluated as potential anticancer compounds in vitro.[11]
Summary
The improvement of the anticancer performance of metalbased agents is an important task of modern chemistry.[1] Among the numerous strategies aimed at enhancing both activity and selectivity of these molecules, conjugation with biologically active molecular fragments targeting tumor cells is very promising.[2−8] In this context, our group has recently investigated Pt(II) complexes in 18 e− trigonal bipyramidal geometry (tbp) containing a sugar-based axial ligand (1 in Figure 1).[9−12]. The results were framed in the light of the key-role played by the sugar portion, whose nature and polarity can affect internalization, the metallodrug cellular pathway, and target recognition.[15−17]
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