Higher generation cationic N,N-ruthenium(II)-ethylene-glycol-derived metallodendrimers: Synthesis, characterization and cytotoxicity

Abstract

A new series of higher generation cationic N,N-chelating, ruthenium(II)-ethylene-glycol metallodendrimers from first-, second-, third- and fourth-generation pyridylimine-based poly(propylene) dendrimer scaffolds of the type, DAB-(NH2)n (where n = 4, 8, 16 or 32, DAB = diaminobutane) have been prepared. Four metallodendrimers were synthesized, by first reacting DAB-(NH2)n with 2-pyridinecarboxaldehyde; and subsequently reacting the Schiff-base dendritic ligands with the [(η6-C6H5OCH2CH2OH)RuCl2]2 dimer, via a bridge-splitting reaction. All compounds were fully characterized using numerous spectroscopic and analytical techniques. In vitro anticancer activities of the complexes were evaluated against the A2780 cisplatin-sensitive and A2780cisR cisplatin-resistant human ovarian carcinoma cell lines and against the non-tumorigenic HEK-293 human embryonic kidney cell line, with the largest dendrimer being the most cytotoxic and selective of all the compounds. A mononuclear model analog was prepared to investigate the size dependency of the systems towards the biological activity.