Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds

The rational development of multinuclear arene ruthenium complexes (arene = p-cymene, hexamethylbenzene) from generation 1 (G1) and generation 2 (G2) of 4-iminopyridyl based poly(propyleneimine) dendrimer scaffolds of the type, DAB-(NH2)n (n = 4 or 8, DAB = diaminobutane) has been accomplished in order to exploit the ‘enhanced permeability and retention’ (EPR) effect that allows large molecules to selectively enter cancer cells. Four compounds were synthesised, i.e. [{(p-cymene)RuCl2}4G1] (1), [{(hexamethylbenzene)RuCl2}4G1] (2), [{(p-cymene)RuCl2}8G2] (3), and [{(hexamethylbenzene)RuCl2}8G2] (4), by first reacting DAB-(NH2)n with 4-pyridinecarboxaldehyde and subsequently metallating the iminopyridyl dendrimers with [(p-cymene)RuCl2]2 or [(hexamethylbenzene)RuCl2]2. The related mononuclear complexes [(p-cymene)RuCl2(L)] (5) and [(hexamethylbenzene)RuCl2(L)] (6) were obtained in a similar manner from N-(pyridin-4-ylmethylene)propan-1-amine (L). The molecular structure of 5 has been determined by X-ray diffraction analysis and the in vitro anticancer activities of the mono-, tetra- and octanuclear complexes 1–6 studied on the A2780 human ovarian carcinoma cell line showing a close correlation between the size of the compound and cytotoxicity.

First-(G1) and second-generation (G2) arene-ruthenium complexes based on a poly(propylene imine) dendritic scaffold were synthesised. The in vitro anticancer studies of the tetra- and octanuclear dendritic complexes, together with their mononuclear analogues, were evaluated against the A2780 human ovarian carcinoma cell line.Figure optionsDownload as PowerPoint slide