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-C6H4Me)2(μ-SEt2)]2 or cis-[Pt(C6H5)2(SMe2)2] with imines 2-ClC6H4CHNCH2CH2NMe2 (b) or 2-F,6-ClC6H3CHNCH2CH2NMe2 (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.