Physicochemical Studies and Anticancer Potency of Ruthenium η⁶-<i>p</i>-Cymene Complexes Containing Antibacterial Quinolones

Abstract

With the aim of exploring the anticancer properties of organometallic compounds with bioactive ligands, Ru(arene) compounds of the antibacterial quinolones nalidixic acid (<b>2</b>) and cinoxacin (<b>3</b>) were synthesized, and their physicochemical properties were compared to those of chlorido(η⁶-<i>p</i>-cymene)(ofloxacinato-κ²<i>O</i>,<i>O</i>)ruthenium(II) (<b>1</b>). All compounds undergo a rapid ligand exchange reaction from chlorido to aqua species. <b>2</b> and <b>3</b> are significantly more stable than <b>1</b> and undergo minor conversion to an unreactive [(cym)Ru(μ-OH)₃Ru(cym)]⁺ species (cym = η⁶-<i>p</i>-cymene). In the presence of human serum albumin <b>1</b>−<b>3</b> form adducts with this transport protein within 20 min of incubation. With guanosine 5′-monophosphate (5′-GMP; as a simple model for reactions with DNA) very rapid reactions yielding adducts via its N7 atom were observed, illustrating that DNA is a possible target for this compound class. A moderate capacity of inhibiting tumor cell proliferation in vitro was observed for <b>1</b> in CH1 ovarian cancer cells, whereas <b>2</b> and <b>3</b> turned out to be inactive