title: Synthesis, biophysical studies, and antiproliferative activity of platinum(II) complexes having 1,2-bis(aminomethyl)carbobicyclic ligands.
abstract: A selected chemical library of six platinum(II) complexes having 1,2-bis(aminomethyl)carbobicyclic ligands were synthesized after a rational design in order to evaluate their antiproliferative activity and the structure-activity relationships. The cytotoxicity studies were performed using cancer cell lines sensitive (A2780) and resistant (A2780R) to cisplatin. Excellent cytotoxicity was observed for most of complexes, which presented better resistance factors than cisplatin against the A2780R cell line. The interaction of these complexes with DNA, as the target biomolecule, was evaluated by several methods: DNA-platinum binding kinetics, changes in the DNA melting temperature, evaluation of the unwinding angle of supercoiled DNA, evaluation of the interstrand cross-links, and replication mapping. The kinetics of the interaction with glutathione was also investigated to better understand the resistant factors observed for the new complexes.
authors.affiliation: Department of Organic Chemistry, University of Barcelona, Martí i Franquès 1-11, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: de Mier-Vinué
authors.forename: Marina
authors.initials: M
authors.lastname: Gay
authors.forename: Angel M
authors.initials: AM
authors.lastname: Montaña
authors.forename: Rosa-Isabel
authors.initials: RI
authors.lastname: Sáez
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
authors.forename: Jana
authors.initials: J
authors.lastname: Kasparkova
authors.forename: Oldrich
authors.initials: O
authors.lastname: Vrana
authors.forename: Pavla
authors.initials: P
authors.lastname: Heringova
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
authors.forename: Angela
authors.initials: A
authors.lastname: Boccarelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Coluccia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008024:Ligands; D010984:Platinum; D044366:Transition Temperature
chemical_list: D000970:Antineoplastic Agents; D001643:Bridged Bicyclo Compounds; D002614:Chelating Agents; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D003959:Diamines; D008024:Ligands; D010984:Platinum; D004247:DNA; D005978:Glutathione; D002945:Cisplatin