title: Pt(II) complexes with (N,N') or (C,N,E)(-) (E=N,S) ligands: cytotoxic studies, effect on DNA tertiary structure and structure-activity relationships.
abstract: The cytotoxic activity of two series of platinum(II) complexes containing the polyfunctional imines R(1)-CHN-R(2) [R(1)=phenyl or ferrocenyl unit and R(2)=(CH2)n-CH2-NMe2 where n=1 or 2) (1 and 2) or C6H4-2-SMe (3)] acting as a bidentate (N,N') (4-7) or terdentate [C(phenyl or ferrocenyl),N,N'](-) (8-10) or [C(ferrocenyl),N,S](-) ligand (11) in front of A549 lung, MDA-MB231 breast and HCT116 colon human adenocarcinoma cell lines is reported. The results reveal that most of the platinum(II) complexes are active against the three assayed lines and compounds 6, 7 and the platinacycles 10 and 11 exhibit a remarkable antiproliferative activity, even greater than cisplatin itself, in the cisplatin resistant HCT116 human cancer cell line. Electrophoretic DNA migration studies showed that most of them modify the DNA tertiary structure in a similar way as the reference cisplatin. Solution studies of a selection of the most relevant complexes have also been performed in order to test: (a) their stability in the aqueous biological medium and/or the formation of biologically active species and (b) their proclivity to react with 9-methylguanine (9-MeG), as a model nucleobase. Computational studies at DFT level have also been performed in order to explain the different solution behaviour of the complexes and their proclivity to react with the nucleobase.
authors.affiliation: Departament de Química Inorgànica, Facultat de Química, Universitat de Barcelona, Diagonal 645, E-08028 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albert
authors.forename: Ramon
authors.initials: R
authors.lastname: Bosque
authors.forename: Margarita
authors.initials: M
authors.lastname: Crespo
authors.forename: Jaume
authors.initials: J
authors.lastname: Granell
authors.forename: Concepción
authors.initials: C
authors.lastname: López
authors.forename: Roldán
authors.initials: R
authors.lastname: Cortés
authors.forename: Asensio
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Josefina
authors.initials: J
authors.lastname: Quirante
authors.forename: Carme
authors.initials: C
authors.lastname: Calvis
authors.forename: Ramon
authors.initials: R
authors.lastname: Messeguer
authors.forename: Laura
authors.initials: L
authors.lastname: Baldomà
authors.forename: Josefa
authors.initials: J
authors.lastname: Badia
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004247:DNA / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D010984:Platinum; D004247:DNA; D002945:Cisplatin