title: Antiproliferative properties and biomolecular interactions of three Pd(II) and Pt(II) complexes.
abstract: Three Pd(II) and Pt(II) complexes with chelating mono(imidazolin-2-imine) and bis(imidazolin-2-imine) ligands i.e. [Pd(DMEAImiPr)Cl2] (1) (DMEAImiPr, 2-(1,3-diisopropyl-4,5-dimethylimidazolin-2-imine)ethan-1-dimethylamine), [Pd(DACH(ImiPr)2)Cl2] (2) (DACH(ImiPr)2, N,N'-(cyclohexane-1,2-diyl)bis(1,3-diisopropyl-4,5-dimethylimidazolin-2-imine)) and [Pt(DMEAImiPr)Cl2] (3), are evaluated here as potential cytotoxic and anticancer agents. An acceptable solution behaviour was found for the three study compounds in terms of solubility and stability. Notably, the three metal complexes demonstrated moderate to high cytotoxic properties in selected cancer cell lines (liquid and solid tumor). To gain deeper mechanistic insight, the reactivity of the study complexes with model DNA oligos and protein molecules was investigated through spectrometric and spectroscopic methods; in both cases adduct formation was clearly documented by ESI-MS measurements. The binding of these metal complexes to calf thymus DNA (CT-DNA) was further examined by absorption (UV-Vis) and emission spectral studies (Ethidium bromide displacement studies, EtBr). Overall, the studied complexes 1-3 exhibited a remarkable DNA binding ability that might be linked to the observed cytotoxic effects. Interestingly our results revealed that DNA binding, as well as anticancer activity of 1-3 follows the order 2>3>1. The implications of these findings are discussed.
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pratesi
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, P. O. Box 60, 34000 Kragujevac, Serbia.
authors.forename: Jovana
authors.initials: J
authors.lastname: Bogojeski
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Banchini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale G.B. Morgagni 50, Florence, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pillozzi
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: luigi.messori@unifi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, P. O. Box 60, 34000 Kragujevac, Serbia. Electronic address: bugarcic@kg.ac.rs.
authors.forename: Živadin D
authors.initials: ŽD
authors.lastname: Bugarčić
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009841:Oligonucleotides; D009944:Organoplatinum Compounds; D010165:Palladium
keywords: Anticancer drugs; Ct-DNA; Platinum and palladium compounds