title: Seven-membered cycloplatinated complexes as a new family of anticancer agents. X-ray characterization and preliminary biological studies.
abstract: A series of seven-membered cyclometallated Pt(II) complexes containing a terdentate [C,N,N'] ligand (1a-1c and 2a-2c) have been developed as potential monofunctional DNA binding agents. By reactions of cis-[Pt(4-C(6)H(4)Me)(2)(μ-SEt(2))](2) or cis-[Pt(C(6)H(5))(2)(SMe(2))(2)] with imines 2-ClC(6)H(4)CHNCH(2)CH(2)NMe(2) (b) or 2-F,6-ClC(6)H(3)CH=NCH(2)CH(2)NMe(2) (c) the new compounds 1b, 1c and 2c were synthesized and characterized. Complex 1b and 1c were further characterized by X-ray crystallography. The cytotoxicity assessment of the seven-membered platinacycles 1 (1a-1c) and 2 (2a-2c) against a panel of human cancer cell lines (A549 lung, HCT116 colon, and MDA MB231 breast adenocarcinomas) revealed that the six cycloplatinated complexes exhibit a remarkable antiproliferative activity, even greater than cisplatin in the three human cancer cell lines. From a pharmacological point of view, platinacycles 1 (1a-1c) and 2 (2a-2c) may represent compounds for a new class of antitumor drugs. Electrophoretic DNA migration studies showed that all of them modify the DNA tertiary structure. Induction of S-G2/M arrest and apoptosis were also observed for one of the representative compounds (1c) of the series.
authors: Department of Biochemistry and Molecular Biology, Faculty of Biology, Institute of Biomedicine of University of Barcelona (IBUB) and IDIBAPS, Unit Associated with CSIC, Diagonal 643, 08028 Barcelona, Spain.
authors: Roldán
authors: R
authors: Cortés
authors: Margarita
authors: M
authors: Crespo
authors: Laia
authors: L
authors: Davin
authors: Raquel
authors: R
authors: Martín
authors: Josefina
authors: J
authors: Quirante
authors: Daniel
authors: D
authors: Ruiz
authors: Ramon
authors: R
authors: Messeguer
authors: Carme
authors: C
authors: Calvis
authors: Laura
authors: L
authors: Baldomà
authors: Josefa
authors: J
authors: Badia
authors: Mercè
authors: M
authors: Font-Bardía
authors: Teresa
authors: T
authors: Calvet
authors: Marta
authors: M
authors: Cascante
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004278:DNA, Superhelical / Q000378:metabolism; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D009944:Organoplatinum Compounds