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Evaluation of cytoxicity of glycosyl uridine derivatives

Katarzyna Papaj 1Roman Komor 1Gabriela Pastuch-Gawołek 1Aleksandra Rusin 2Wiesław Szeja 1

1. Silesian University of Technology, Department of Organic Chem., Bioorganic Chem. and Biotechnol., Krzywoustego 4, Gliwice 44-100, Poland
2. Maria Skłodowska-Curie Memorial Center and Institute of Onkology, Center for Translational Research and Molecular Biology of Cancer, Gliwice Branch, Gliwice 44-100, Poland

Abstract
Glycosyltransferases (GTs) are enzymes responsible for formation of the glycosidic bond by transfer of sugar unit from glycosyl donor to glycosyl acceptor. In cells these enzymes are responsible for synthesis of glycoconjugates and they precipitate in glycosylation of cell surface proteins. Inhibition of GTs activity may contribute to decrease of cancer cell proliferation as a result disorders in biosynthesis of glycoconjugates [1,2]. Many efforts were made in different laboratories to obtain new inhibitors of GTs. Uridine derivatives are very promising compounds for potential antiviral and anticancer activity. In our department series of analogues of UDP-glucose or UDP-galactose were designed and synthesized. Indicated that some of these derivatives decrease the number of cells infected by classical swine fever virus (CSFV) and its insignificantly toxic to normal cells.    

The aim of this work is determination of cytotoxicity of uridine derivatives. We indicated toxicity of the tested compounds in HCT 116 and DU 145 cell lines with use of MTT assay. Cells were plated in 96-well plate at the density 2*103 (HCT 116) or 3*103 (HCT 116) cells per well and grown for 24h. Then, the cells were treated by the tested compounds at growing series of concentrations: 0.01, 0.1, 0.5, 1.0, 5.0, 10.0, 25.0, 50.0 and 100μM for 72h. After 3h incubation with MTT substrate (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) the absorbance of samples was measured spectrophotometrically with a microplate reader at 570nm wavelength. 

Our result indicate that described compounds did not affect proliferation of the tested cell lines.

Acknowledgement:

Research studies part-financed by the European Union within the European Regional Development Fund (POIG.01.01.02-14-102/09). Roman Komor received a scholarship under the project DoktoRIS - Scholarship Program for Innovative Silesia.

References:

[1] C. Breton; L. Šnajdrová; C. Jeanneau, J. Koca, A. Imberty, Glycobiology, 2006, 16, 29R–37R

[2] K. Hosoguchi, T. Maeda,J. Furukawa, Y. Shinohara, H. Hinou, M. Sekiguchi, H. Togame, H. Takemoto, H. Kondo, S.-I. Nishimura, J. Med. Chem. 2010, 53, 5607–5619  

 

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Presentation: Poster at IX Multidyscyplinarna Konferencja Nauki o Leku, by Katarzyna Papaj
See On-line Journal of IX Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2014-03-13 21:35
Revised:   2014-05-02 16:58