Djinović Vesna, Momcilović Miljana, Grgurić-Sipka Sanja, Trajković Vladimir, Mostarica Stojković Marija, Miljković Djordje, Sabo Tibor
Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia and Montenegro.
J Inorg Biochem. 2004 Dec;98(12):2168-73. doi: 10.1016/j.jinorgbio.2004.10.007.
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.
合成了一类新型的化学式为K[Ru(sar)₂Cl₂]·12H₂O和K₂[Ru(dmgly)Cl₄]·2H₂O的钌(III)配合物，其含有双齿螯合物N-甲基甘氨酸（肌氨酸，sar）或N,N-二甲基甘氨酸（dmgly）以及额外的氯配体。这些配合物是通过氯化钌(III)与相应的双齿配体直接反应，随后加入碱（KOH）得到的。通过元素分析、红外光谱和电子吸收光谱对这些新配合物进行了表征。由于星形细胞瘤是所有脑肿瘤中最常见的，但仍然很难治疗，我们研究了新合成的钌基配合物以及早期合成的类似物铂(IV)配合物[Pt(dmgly)₂Cl₂]、[Pt(sar)₂Br₂]和[Pt(dmgly)₂Br₂]对大鼠星形细胞瘤C6细胞的体外影响。在这些配合物中，只有K₂[Ru(dmgly)Cl₄]·2H₂O和[Pt(dmgly)₂Br₂]显著抑制了未汇合的C6细胞的活力。此外，只有配合物K₂[Ru(dmgly)Cl₄]·2H₂O能够降低汇合的C6培养物中的活力。重要的是，这种配合物对原代大鼠星形胶质细胞或巨噬细胞无毒。考虑到合适的化疗应该对肿瘤细胞有效而不损害正常组织，配合物K₂[Ru(dmgly)Cl₄]·2H₂O可能是开发抗星形细胞瘤治疗药物的有前景的试剂。
