Özalp Yaman, ŞenizOzalp-Yaman, Senizde Hoog, PaulAmadei, GiulioPitie, MargueriteGamez, PatrickDewelle, JaniqueReedijk, JanChemical Engineering2024-07-052024-07-052008430947-65391521-376510.1002/chem.2007020212-s2.0-53849099656https://doi.org/10.1002/chem.200702021https://hdl.handle.net/20.500.14411/1027Patrick Gamez, FRSC/0000-0003-2602-9525; MEUNIER, Bernard/0000-0003-2200-7142; Reedijk, Jan/0000-0002-6739-8514; Ozalp Yaman, Seniz/0000-0002-4166-0529The 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), I and 6 stimulate different cellular responses.eninfo:eu-repo/semantics/closedAccessantitumor agentscisplatinDNA cleavageplatinumprimer extensionArticleQ2141134183426WOS:00025523020002118293353