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 6H 4Me) 2(μ-SEt 2)] 2 or cis-[Pt(C 6H 5) 2(SMe 2) 2] with imines 2-ClC 6H 4CHNCH 2CH 2NMe 2 (b) or 2-F,6-ClC 6H 3CHNCH 2CH 2NMe 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. © 2012 Elsevier Masson SAS. All rights reserved.