In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N’-di-2-propanoic Acid

Author(s): Bojana B. Zmejkovski , Nebojša Pantelić , Lana Filipović , Sandra Aranđelović , Siniša Radulović , Tibor J. Sabo , Goran N. Kaluđerović* .

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 17 , Issue 8 , 2017

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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.

Keywords: Platinum complexes, R2eddip ligands, DFT calculations, anticancer activity, apoptosis, cell cycle.

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Article Details

VOLUME: 17
ISSUE: 8
Year: 2017
Page: [1136 - 1143]
Pages: 8
DOI: 10.2174/1871520616666161207155634
Price: $58

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