Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes

Abstract

A novel class of ruthenium (111) complexes of formulas K[Ru(sar)(2)Cl-2] - 1/2HO and K-2[Ru(dmgly)Cl-4] . 1/2H(2)O, containing biden2 tate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dnigly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmglY)(2)Cl-2], [Pt(sar)(2)Br-2] and [Pt(dmgly)(2)Br-2] on rat astrocytoma C6 cells in vitro. Among these complexes only K-2[Ru(dmglY)Cl-4].2H(2)O and [Pt(dMgIY)(2)Br-2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K-2[Ru(dmgly)Cl4] .2H20 was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K,[Ru(dmglY)Cl-4] - 2H(2)O could be a promising agent for developing therapeutics against astrocytomas. (C) 2004 Elsevier Inc. All rights reserved.