The present study describes the
biological evaluation of a library of 59 organo-
selenium compounds as
superoxide (O₂⁻) generators and
cytotoxic agents in human
prostate cancer cells (PC-3) and in breast
adenocarcinoma (MCF-7). In order to corroborate that the
biological activity for
selenium compounds depends on the chemical form, a broad structural variety is presented. These structures include selenocyanates, diselenides, selenoalkyl functional moieties and eight newly synthesized symmetrically substituted dithioselenites and selenylureas. Eleven of the derivatives tested showed high levels of
superoxide generation in vitro via oxidation of
reduced glutathione (GSH) and nine of them were more catalytic than the reference compound, diselenodipropionic
acid. Eighteen of the library compounds inhibited cell growth more than or similar to reference chemotherapeutic drugs in PC-3 and eleven were more potent
cytotoxic agents than
etoposide in the MCF-7 cell line. Considering both parameters (
superoxide generation and cell cytotoxicity) compounds B1, C6 and C9 displayed the best therapeutic profiles. Considering that many diselenide compounds can generate
superoxide (O₂⁻) in vitro via oxidation of GSH and other
thiols, the analogue B1, that contains a diselenide moiety, was selected for a preliminary mechanistic investigation, which revealed that B1 has apoptogenic effects similar to
camptothecin mediated by
reactive oxygen species (ROS) in
lymphocytic leukemia cells (CCRF-CEM) and affected the MCF-7 cell-cycle in G₂/M and S-phases.