Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex

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)-ethylendiamine-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 caspases (8, 9 and 3) activation and phosphatidylserine externalization. This article is protected by copyright. All rights reserved.