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Platinated Copper(3‐Clip‐Phen) Complexes as Effective DNA‐Cleaving and Cytotoxic Agents
Author(s) -
ÖzalpYaman Şeniz,
de Hoog Paul,
Amadei Giulio,
Pitié Marguerite,
Gamez Patrick,
Dewelle Janique,
Mijatovic Tatjana,
Meunier Bernard,
Kiss Robert,
Reedijk Jan
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200702021
Subject(s) - moiety , platinum , chemistry , stereochemistry , dna , cytotoxicity , cisplatin , cleavage (geology) , heteronuclear molecule , ligand (biochemistry) , nuclease , biochemistry , in vitro , nuclear magnetic resonance spectroscopy , biology , receptor , paleontology , chemotherapy , fracture (geology) , genetics , catalysis
The synthesis and biological activity of three heteronuclear platinum–copper complexes based on 3‐Clip‐Phen are reported. These rigid complexes have been designed to alter the intrinsic mechanism of action of both the platinum moiety and the Cu(3‐Clip‐Phen) unit. The platinum centers of two of these complexes are coordinated to a 3‐Clip‐Phen moiety, an ammine ligand and two chlorides, which are either cis or trans to each other. The third complex comprises two 3‐Clip‐Phen units and two chloride ligands bound in a trans fashion to the platinum ion. DNA‐cleavage experiments show that the complexes are highly efficient nuclease agents. In addition, a markedly difference in their aptitude to perform direct double‐strand cleavage is observed, which appears to be strongly related to the ability of the platinum unit to coordinate to DNA. Indeed, complex 6 is unable to coordinate to DNA, which is reflected by its incapability to carry out double‐strand breaks. Nonetheless, this complex exhibits efficient DNA‐cleavage activity, and its cytotoxicity is high for several cell lines. Complex 6 shows better antiproliferate activity than both cisplatin and Cu(3‐Clip‐Phen) toward most cancer cell lines. Furthermore, the cytotoxicity observed for 1 is for most cell lines close to that of cisplatin, or even better. Cu(3‐Clip‐Phen) induces very low cytotoxic effects, but a marked migratory activity. Complex 6 presents DNA‐cleavage properties comparable to the one of Cu(3‐Clip‐Phen), but it does not show any migratory activity. Interestingly, both Cu(3‐Clip‐Phen) and 6 induces vacuolisation processes in the cell in contrast to complex 1 and cisplatin. Thus, the four complexes cisplatin tested, Cu(3‐Clip‐Phen), 1 and 6 stimulate different cellular responses.