title: Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex.
abstract: This study presents the synthesis, characterization, and antitumor action of five new Pt(II) halogenido, chlorido, and iodido complexes with edda type of ligands. (S,S)-Ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid dihydrochloride and its methyl, ethyl, and n-propyl esters were prepared according to the previously reported procedure. All investigated complexes were characterized by IR, ESI-MS (1H,13C, and HMBC) NMR spectroscopy, and elemental analysis. Their cytotoxic action was investigated in four human tumor cell lines: promyelocytic (HL-60) and lymphocytic (REH) leukemia, glioma (U251), and lung carcinoma (H460). Cell viability was assessed by acid phosphatase and LDH assay, while oxidative stress and cell death parameters were analyzed by flow cytometry. The results showed that novel Pt(II) complexes exhibited antitumor action superior to precursor ligands, with iodido complexes being more efficient than corresponding chlorido complexes. Human promyelocytic cell line (HL-60) was the most sensitive to antitumor action of all investigated substances and was used for investigation of the underlying mode of antileukemic action. The investigated Pt(II) complexes showed more potent antileukemic action than corresponding Pt(IV) complex, through induction of oxidative stress and apoptosis, evidenced by caspase (8, 9, and 3) activation and phosphatidylserine externalization.
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Misirlić Denčić
authors.affiliation: Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Poljarević
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Andjelka M
authors.initials: AM
authors.lastname: Isakovic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Ivanka
authors.initials: I
authors.lastname: Marković
authors.affiliation: Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.
authors.forename: Tibor J
authors.initials: TJ
authors.lastname: Sabo
authors.affiliation: Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.
authors.forename: Sanja
authors.identifier: 0000-0003-1906-535X
authors.initials: S
authors.lastname: Grgurić-Šipka
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054879:Halogenation; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D008024:Ligands; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005029:Ethylenediamines; D008024:Ligands; D009944:Organoplatinum Compounds; C031234:ethylenediamine
keywords: antileukemic; caspases; edda ligands; phosphatidylserine; platinum(II) complexes