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 (G(1)) and generation 2 (G(2)) 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}(4)G(1)] (1), [{(hexamethylbenzene)RuCl2}(4)G(1)] (2), [{(p-cymene)RuCl2}(8)G(2)] (3), and [{(hexamethylbenzene)RuCl2}(8)G(2)] ( 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. (C) 2009 Elsevier B.V. All rights reserved.