title: In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N'-di-2-propanoic Acid.
abstract: OBJECTIVE
  Platinum(II) and platinum(IV) complexes [PtCln{(S,S)-(i-Am)2eddip}] (n = 2, 4: 1, 2, respectively; (S,S)-(i-Am)2eddip = O,O'-diisoamyl-(S,S)-ethylenediamine-N,N'-di-2-propanoate) were synthesized and characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy and mass spectrometry.
  
  
  METHODS
  Quantum chemical calculations were used to predict formed isomers of 1 and 2. Furthermore, reduction of 2 with ascorbic acid was followed by time-dependant 13C NMR spectroscopy in order to enable assignation of the formed isomers for complex 1. In vitro cytotoxic activity was determined for 1 and 2 on a panel of five human tumor cell lines derived from cervix adenocarcinoma (HeLa), alveolar basal adenocarcinoma (A549), breast adenocarcinoma (MDA-453), colorectal cancer (LS 174), erythromyeloblastoid leukemia (K562), as well as one non-malignant human lung fibroblast cell line (MRC-5), using MTT assay.
  
  
  RESULTS
  Both complexes exhibited high (2 against K562: IC50 = 5.4 μM), more active than cisplatin, to moderate activity (1). Both complexes caused considerable decrease of cell number in K562 cells in G1, S and G2 phases, concordantly increasing subpopulation in sub-G1 fraction. Morphological analysis of K562 cell death induced by platinum(II/IV) complexes indicate apoptosis.
authors.affiliation: Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Bojana B
authors.initials: BB
authors.lastname: Zmejkovski
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade-Zemun, Serbia.
authors.forename: Nebojša
authors.initials: N
authors.lastname: Pantelić
authors.affiliation: Institute of Oncology and Radiology, 11000 Belgrade, Serbia.
authors.forename: Lana
authors.initials: L
authors.lastname: Filipović
authors.affiliation: Institute of Oncology and Radiology, 11000 Belgrade, Serbia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Aranđelović
authors.affiliation: Institute of Oncology and Radiology, 11000 Belgrade, Serbia.
authors.forename: Siniša
authors.initials: S
authors.lastname: Radulović
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Tibor J
authors.initials: TJ
authors.lastname: Sabo
authors.affiliation: Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale). Germany.
authors.forename: Goran N
authors.initials: GN
authors.lastname: Kaluđerović
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000737:chemistry / Q000494:pharmacology*; D005029:Ethylenediamines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D005029:Ethylenediamines; D009944:Organoplatinum Compounds; C000622265:ethylenediamine-N,N'-di-2-propanoic acid diisoamyl ester; D000409:Alanine
keywords: DFT calculations; Platinum complexes; R2eddip ligands; anticancer activity; apoptosis; cell cycle