Reactivity and biological properties of a series of cytotoxic PtI2(amine)2 complexes, either cis or trans configured.
Six diiodido-diamine platinum(II) complexes, either cis or trans 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 trans isomers being, generally, more effective than their cis 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 trans complexes preferentially release their iodide ligands upon biomolecule binding, while the cis 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.
Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
Luigi
L
Messori
Leticia
L
Cubo
Chiara
C
Gabbiani
Amparo
A
Álvarez-Valdés
Elena
E
Michelucci
Giuseppe
G
Pieraccini
Carla
C
Ríos-Luci
Leticia G
LG
León
José M
JM
Padrón
Carmen
C
Navarro-Ranninger
Angela
A
Casini
Adoración G
AG
Quiroga
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D010984:Platinum