New chiral camphane-derived benzisoselenazol-3(2H)-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives was evaluated and compared to the reactivity of a series of N-amino acid benzisoselenazol-3(2H)-ones obtained by a modified procedure involving the improved synthesis and isolation of the diseleno bis(dibenzoic) acid. The most efficient peroxide scavengers, N-bornyl and N-leucine methyl ester benzisoselenazol-3(2H)-ones, were further evaluated as cytotoxic agents on four cancer cell lines (MCF-7, HEP G2, HL 6, and DU 145) and normal cell line PNT1A. The highest antiproliferative potential was evaluated for two compounds bearing a 3-methylbutyl carbon chain, N-leucine methyl ester and N-3-methylbutyl benzisoselenazol-3(2H)-ones.

Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, including cytostatic and cytotoxic action against tumor cells. In this study, the cytotoxic effect and anticancer mechanism of action of two organoselenium compounds— (N-allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one) (N-(3-mb)-BS)—were investigated on two phenotypically different prostate cancer cell lines DU 145 and PC-3. The influence of analyzed compounds on the viability parameter was also assessed on normal prostate cell line PNT1A. The results showed that both organoselenium compounds (OSCs) efficiently inhibited cancer cell proliferation, whereas normal PNT1A cells were less sensitive to the analazyed ebselen analouges. Both OSCs induced G2/M cell cycle arrest and prompted cell death through apoptosis. The detection of cleaved Poly (ADP-ribose) Polymerase (PARP) confirmed this. In addition, N-allyl-BS and N-(3-m)-b-BS increased the level of reactive oxygen species (ROS) formation, however only N-allyl-BS induced DNA damage. Based on our data, we assume that OSCs’ anticancer action can be associated with oxidative stress induction and inactivation of the Akt- dependent signalling pathway. In conclusion, our data demonstrate that ebselen derivatives showed strong cytotoxic efficiency towards prostate cancer cells and may be elucidated as a novel, potent anticancer agent.

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.

     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.