Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex
Isaković, Anđelka M.
Article (Accepted Version)
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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 (H-1, C-13, 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 (H...L-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.
Keywords:antileukemic / caspases / edda ligands / phosphatidylserine / platinum(II) complexes
Source:Chemical Biology and Drug Design, 2017, 90, 2, 262-271
- Wiley, Hoboken
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-172035)
- Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-41025)
- This is the peer-reviewed version of the following article: Misirlić Denčić, S.; Poljarević, J.; Isakovic, A. M.; Marković, I.; Sabo, T. J.; Grgurić-Šipka, S. Antileukemic Action of Novel Diamine Pt(II) Halogenido Complexes: Comparison of the Representative Novel Pt(II) with Corresponding Pt(IV) Complex. Chemical Biology and Drug Design 2017, 90 (2), 262–271. https://doi.org/10.1111/cbdd.12945
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3121