Novel ruthenium complex K2[Ru(dmgly)Cl4].2H2O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes.

A novel class of ruthenium (III) complexes of formulas K[Ru(sar)2Cl2].12H2O and K2[Ru(dmgly)Cl4].2H2O, containing bidentate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dmgly) 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)2Cl2], [Pt(sar)2Br2] and [Pt(dmgly)2Br2], on rat astrocytoma C6 cells in vitro. Among these complexes only K2[Ru(dmgly)Cl4].2H2O and [Pt(dmgly)2Br2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K2[Ru(dmgly)Cl4].2H2O 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 K2[Ru(dmgly)Cl4].2H2O could be a promising agent for developing therapeutics against astrocytomas.

Synthesis and structures of novel 1-methylcytosinato-bridged (ethylenediamine)platinum(II) and platinum(III) dinuclear complexes.

The reaction of [Pt(en)(H(2)O)(2)](2+) with 1 equivalent of 1-methylcytosine at an initial pH of 6 ultimately led to the 1-methylcytosinato-bridged (ethylenediamine)platinum(II) dimer, [(en)Pt(MetCyt-H)(2)Pt(en)](NO(3))(2) (1). The species during the reactions prior to formation of 1 have been investigated by using (195)Pt NMR spectroscopy. From the reaction mixture the [Pt(en)(MetCyt)(2)](NO(3))(2) complex (3) could be isolated and structurally characterized. A rational synthesis of 1 was also achieved by dimerization of [Pt(en)(MetCyt)(H(2)O)](NO(3))(2). According to X-ray structure analysis, the Pt-Pt distance of 2.9816(3) A in 1 is well comparable with the corresponding value found in the cis-diammineplatinum(II) analog (2.981(2) A). Oxidation of 1 with K(2)S(2)O(8) led to the symmetrically sulfate-capped diplatinum(III) complex with two ethylenediamine ligands equatorially bound to the two Pt atoms ht-[(SO(4))(en)Pt(MeCyt-H)(2)Pt(en)(SO(4))] (5), as established by X-ray crystallography. When the oxidation was carried out in the presence of HClO(4), the formation of the hydroxido/aqua ht-1-methylcytosinato bridged (en)Pt(III) dimer ht-[H(2)O(en)Pt(MetCyt-H)(2)Pt(en)OH](ClO(4))(3) (6) was observed, as supported by elemental and X-ray structure analysis. In the structure of 6, two ethylenediamine ligands are differently bound to the two Pt centers: one of them equatorially while the second one caps the opposite axial site of the diplatinum(III) core. The Pt-Pt distances in the platinum(iii) dimers are 2.5982(4) in 5 and 2.5569(3) A in 6.

Novel platinum(IV) complexes induce rapid tumor cell death in vitro.

The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum-based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress-independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy.