Reactivity and Biological Properties of a Series of Cytotoxic PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different modes of action for these new Pt­(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that <i>trans</i> complexes preferentially release their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles

Reactivity and Biological Properties of a Series of Cytotoxic PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different modes of action for these new Pt­(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that <i>trans</i> complexes preferentially release their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles