Title:In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N’-di-2-propanoic Acid
Volume: 17
Issue: 8
Author(s): Bojana B. Zmejkovski, Nebojša Pantelić, Lana Filipović, Sandra Aranđelović, Siniša Radulović, Tibor J. Sabo and Goran N. Kaluđerović*
Affiliation:
- Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale),Germany
Keywords:
Platinum complexes, R2eddip ligands, DFT calculations, anticancer activity, apoptosis, cell cycle.
Abstract: Aims: 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.
Method: 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.
Result: 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.
