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N-substituted ebselen derivatives and corresponding diselenides as the potential antitumor agents in prostate cancer model
* 1 , * 1 , 2 , 2
1  Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk
2  Department of Organic Chemistry, Nicolaus Copernicus University in Torun, Poland

Published: 02 November 2015 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1

     N-substituted benzisoselenazol-3(2H)-ones have been shown to have a broad spectrum of biological activities including anti-inflammatory and antioxidant activity and are believed to be a novel anticancer agents. Ebselen derivatives possess the ability to mimic the capacity of glutathione peroxidase (GPx), an antioxidant enzyme which removes the excess of reactive oxygen species and prevents from oxidative stress.

     The aim of the study was to test the antiproliferative and cytotoxic activity of benzisoselenazolone derivatives and to select those with antitumor activity.

     Prostate cancer cell lines with genetic background (PC-3, DU145) were treated with different concentrations of bensisoselenazolone analogs and corresponding diselenides. The cytotoxity and inhibition of cell proliferation were identified by Sulforhodamine B assay (SRB). The changes in level of Akt were evaluated using Western blot method.

     We observed that among twenty structurally different ebselen derivatives, four of them demonstrated antiproliferative activity at 40 µM concentration. Three of them were more cytotoxic to DU145 cell lines than to PC-3 and this data correlates with basal Akt activity, which is higher in PC-3 cells. On the other hand the cytotoxicity of N-butyl-1,2-benzisoselenazol-3(2H)-one was similar in both cell lines indicating different mode of action compared to other three selenocompounds. In conclusion, our initial data demonstarte the anticancer efficiency of benzisoselenazolones and corresponding diselenides.

Keywords: prostate cancer, benzisoselenazolone analogs, kinase Akt, antioxidant activity