title: Novel ruthenium complex K2[Ru(dmgly)Cl4].2H2O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes.
abstract: 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.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia and Montenegro.
authors.forename: Vesna
authors.initials: V
authors.lastname: Djinović
authors.forename: Miljana
authors.initials: M
authors.lastname: Momcilović
authors.forename: Sanja
authors.initials: S
authors.lastname: Grgurić-Sipka
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajković
authors.forename: Marija
authors.initials: M
authors.lastname: Mostarica Stojković
authors.forename: Djordje
authors.initials: D
authors.lastname: Miljković
authors.forename: Tibor
authors.initials: T
authors.lastname: Sabo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects*; D001254:Astrocytoma / Q000188:drug therapy*; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D064420:Drug-Related Side Effects and Adverse Reactions; D006131:Growth Inhibitors / Q000494:pharmacology; D008024:Ligands; D009569:Nitric Oxide / Q000032:analysis; D009573:Nitrites / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology*; D013053:Spectrophotometry / Q000379:methods; D013055:Spectrophotometry, Infrared; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D008024:Ligands; D009573:Nitrites; D009942:Organometallic Compounds; D009569:Nitric Oxide; D010984:Platinum; D012428:Ruthenium