Abstract
Dinuclear ruthenium complexes were shown to exhibit strong antiproliferative properties in human tumor cell lines. In order to extend the structure−activity relationships (SARs), a series of new RuII(arene)X complexes (X = Cl, Br, I) linked by pyridinone-based spacers were synthesized and assayed for their in vitro antineoplastic effect. The SARs were established in terms of the arene ligand, the leaving group (the halide ligand), and the nature and number of the metal centers. It was demonstrated that, besides the previously shown effect of the spacer length, the nature of the metal center has the biggest influence on the in vitro anticancer activity. The halide ligand had no effect on the cytotoxicity, due to rapid formation of the same aquation product for all evaluated compounds. Furthermore, nearly identical activity was observed when varying the arene ligand from p-cymene to biphenyl. However, the number of metal centers was found to be important, with the dinuclear compound being more active than the analogous mono- and trinuclear species.
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