The CellScan technology for in vitro studies on novel platinum complexes with organoarsenic ligands

Abstract

The present paper examines one of the multiple uses of the CellScan technique, its utilization in the biological evaluation of novel compounds, in order to improve the methods concerning the prediction of their anti-proliferative effects and application as anti-cancer drugs. The CellScan is a laser scanning static cytometer, enabling repetitive spectroscopic measurements in intact living cells. The detection of cell viability and apoptosis is possible, based on the transformations that occur in the cytoplasm matrix of tumour cells influenced by cytotoxic compounds. The measurement of fluorescence changes, due to this phenomenon, is possible with the CellScan system. The potential of this technology to detect the in vitro effects of the inhibitory molecules on tumour cells was demonstrated, making this method a valuable tool for chemosensitivity tests. We synthesized and fully characterised three novel platinum complexes of tertiary arsine ligands: trans-[PtI2(2-iPrOC6H4AsPh2)2] (), trans-[PtCl2(2-MeOC6H4AsPh2)2] () and cis-[PtCl2(2-HOC6H4AsPh2)2] (). The three compounds are biologically active against tumour cells and their cytotoxicity is comparable with standard drugs. Measurements using the CellScan technology correlate well with the results provided by other bioassay methods.

Antiproliferative effect and genotoxicity of novel synthesized palladium complexes with organoarsenic ligands

“…Cytotoxicity of these palladium complexes is comparable with the antitumor activity against MLS cells of two widely used drugs: carboplatin (13.75 lM) and oxaliplatin (18.4 lM). In comparison with the similar platinum complexes, with the same organoarsenic ligands, palladium complexes show a slightly lower cytotoxicity, exception being complex 2, which is more active like platinum compounds [15] against MLS cells.…”

“…Previously, we have tested a group of platinum complexes, where similar organoarsenic ligands are coordinated to the metal center [15] and which exhibited an important biologic effect. Based on these studies, we planed to elucidate also the cytotoxicity of complexes 1, 2 and 3, considering that the only difference between the two classes of compounds is the metal center.…”

“…Previous studies of platinum complexes with similar tertiary arsines, describe as well the static cytometry [15]. The histograms provided by the CellScan system contain FP data (for each cell individually) and also a statistic regarding the whole population.…”

“…Based on the promising results obtained with three platinum complexes, which exhibit antitumor activity [15], we synthesized and characterized palladium complexes with analogous tertiary organoarsenic ligands and we tested their antiproliferative activity and their capacity to induce apoptosis. A new method to evaluate the antiproliferative effect and apoptosis induction capacity, the CellScan technology, was already applied to evaluate the biologic 0162-0134/$ -see front matter Ó 2009 Elsevier Inc. All rights reserved.…”

Metrological approaches to drug development. Fast screening using universal biosensors at the stage of drug development

“…These biosensors can be used in pharmaceutics for functional screening at the stage of drug design and discovery [31] and for predictive screening at the stage of planning the targeted synthesis and determination of the mechanism of action of the biologically active substance [32], and for toxicity predictions over a wide concentration range without animal experiments [33,34].…”