title: Synthesis and in vitro anticancer activity of ruthenium-cymene complexes with cyclohexyl-functionalized ethylenediamine-N,N'-diacetate-type ligands.
abstract: Herein we describe the synthesis, characterization, and anticancer activity of novel p-cymeneruthenium(II) complexes containing methyl, ethyl, n-propyl, and n-butyl esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, (1)H, and (13)C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL-60, K562, and REH cells (IC(50): 1.0-20.2 μM), with the n-butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n-butyl ester complex is more effective against leukemic patients' blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of Ru(II)-based compounds.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Savić
authors.forename: Marija
authors.initials: M
authors.lastname: Dulović
authors.forename: Jelena M
authors.initials: JM
authors.lastname: Poljarević
authors.forename: Sonja
authors.initials: S
authors.lastname: Misirlić-Denčić
authors.forename: Maja
authors.initials: M
authors.lastname: Jovanović
authors.forename: Andrija
authors.initials: A
authors.lastname: Bogdanović
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajković
authors.forename: Tibor J
authors.initials: TJ
authors.lastname: Sabo
authors.forename: Sanja
authors.initials: S
authors.lastname: Grgurić-Šipka
authors.forename: Ivanka
authors.initials: I
authors.lastname: Marković
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology*; D005029:Ethylenediamines / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005029:Ethylenediamines; D008024:Ligands; C031234:ethylenediamine; D012428:Ruthenium