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Medicinal Chemistry


ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Evaluation of the Cytotoxic and Pro-Apoptotic Activities of Eu(III) Complexes with Appended DNA Intercalators in a Panel of Human Malignant Cell Lines

Author(s): Georgi Momekov, Todor Deligeorgiev, Aleksey Vasilev, Kalina Peneva, Spiro Konstantinov and Margarita Karaivanova

Volume 2, Issue 5, 2006

Page: [439 - 445] Pages: 7

DOI: 10.2174/157340606778250234

Price: $65


A series of 8 europium (III) tris-β-diketonates with common formula Eu(L)3Int, where L is acetyl acetone, thenoyltrifluoroacetone, benzoylacetone, dibenzoylmethane and Int is 1,10-phenanthroline or 2,2-bipyridine, together with an analog without intercalating moiety (Eu(III)(acetyl acetone)3(H2O)2) were tested for cytotoxic activity in a panel of human tumor cell lines, using the MTT-dye reduction assay. The panel consisted of the leukemias HL-60, BV-173, SKW- 3, K-562, LAMA-84 and the urinary bladder carcinoma 5637. The tested europium complexes with appended intercalator moieties exhibited profound cytotoxic effects with IC50 values lower or comparable to those of the referent drug cis-DDP, whereby the 1,10-phenanthroline bearing compounds were invariably more active than the corresponding 2,2-bipyridine analogs. The established low cytotoxic potential of Eu(III)(acetyl acetone)3(H2O)2 as compared to its highly potent analogs with either 1,10-phenanthroline or 2,2-bipyridine ligand demonstrated that the abundance of intercalating motif is a mandatory structural prerequisite for optimal activity within this series of cytotoxic agents. Selected compound caused DNA-fragmentation when applied in cytotoxic concentration, which suggests that the induction of programmed cell death (apoptosis) at least partly mediates the cytotoxic effects of tested compounds. Taken together our data give us reason to conclude that the presented Eu(III) complexes represent a unique class of cytotoxic metal coordination compounds and necessitate further detailed evaluation in order to define the structure activity relationships as well as the predominant mode of action. To the best knowledge of the authors this is among the first reports of potent cytotoxic Eu(III) compounds.

Keywords: Europium(III), βdiketone, 1,10-phenanthroline, 2,2'-bipyridine, MTT-assay, apoptosis

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