The applicability of organoselenium compounds in medicinal chemistry arises from their unique biological properties, among which the antioxidant activity seems to be the leading one. Since ebselen (N-phenyl-1,2-benzisoselenazol-3(2H)-one) has been proven to mimic the activity of the antioxidant enzyme glutathione peroxidase GPx, the search for more effective peroxide scavengers has become a ‘hot topic’ in this field of research. Herein, we present the synthesis of N-aryl ebselen derivatives, bearing additional electron donating or electron withdrawing groups in the N-phenyl ring, by two methods: (a) reaction of N-substituted o-iodobenzamides with lithium diselenide, (b) synthesis based on the formation of 2,2-diselenobis(benzoic acid), followed by the conversion to corresponding dichloride and further reaction with amine. Significant improvements in these methodologies are highlighted. All obtained ebselen derivatives were further converted to corresponding diselenides by the treatment with sodium borohydride. The antioxidant potential of the obtained selenium derivatives and conclusions concerning the activity-structure relation are presented.

     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.

In recent years, chalcogenides were widely used as efficient reagents and catalysts to create new carbon-oxygen, carbon-nitrogen and carbon-carbon bonds. Our previous research was focused on developing effective methods for the synthesis of new optically active organosulfur and organoselenium compounds derived from monoterpenes. Satisfying results prompted us to synthesize tellurium analogues. We have developed new methodologies for the synthesis of terpene ditellurides, tellurides, methyl terpenyl tellurides, and phenyl terpenyl tellurides from p-menthane, carane and pinane systems. The synthesis was based on the reaction of sodium telluride, sodium ditelluride, sodium benzenetellurolate, and sodium methanetellurolate with terpene tosylates, chlorides and epoxides. Additionally, terpene tellurides were converted in situ to telluronium ylides, and were used as reagents in asymmetric epoxydation. The best selectivity of epoxidation reaction was achieved for dicaranyl telluride.

N-Substituted benzisoselenazol-3(2H)-ones are well known for their ability to mimic the activity of an important antioxidant enzyme glutathione peroxidase. They eliminate the excess of reactive oxygen and nitrogen species and restore the cells redox homeostasis. In the catalytic cycle they can be easily transformed to diselenides, which also exhibit these unique properties. In this work, we have synthetized a series of N-alkyl benzisoselenazolones and corresponding diselenides. The antioxidant activity of all obtained compounds was evaluated and compared. The connection between the antioxidant properties and the ability to inhibit cancer cells proliferation was evaluated by a cytotoxic activity assay using PC-3 and DU145 cell lines.