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.
Djinović
Vesna
V
Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia and Montenegro.
Momcilović
Miljana
M
Grgurić-Sipka
Sanja
S
Trajković
Vladimir
V
Mostarica Stojković
Marija
M
Miljković
Djordje
D
Sabo
Tibor
T
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
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D008024:Ligands; D009573:Nitrites; D009942:Organometallic Compounds; D009569:Nitric Oxide; D010984:Platinum; D012428:Ruthenium