Synthesis and biological evaluation of organoselenium (NSAIDs-SeCN and SeCF3) derivatives as potential anticancer agents

A series of organoselenium compounds based on the hybridization of nonsteroidal antiinflammatory drugs (NSAIDs) scaffolds and Se functionalities (-SeCN and -SeCF₃) were synthesized and characterized, and evaluated against four types of Cancer cell lines, SW480 (human colon adenocarcinoma cells), HeLa (human cervical Cancer cells), A549 (human lung carcinoma cells), MCF-7 (human breast adenocarcinoma cells). Interestingly, most of the investigated compounds showed active in reducing the viability of different Cancer cell lines. The most active compound 3h showed IC₅₀ values lower than 20 μM against the four Cancer cell lines, particularly to SW480 and MCF-7 with IC 50 values of 4.9 and 3.4 μM, respectively. Furthermore, NSAIDs-SeCN derivatives (2h and 2i) and NSAIDs-SeCF₃ derivatives (3h and 3i) were selected to investigate their ability to induce Apoptosis in MCF-7 cells via modulation the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic Caspase-3 protein. Moreover, the redox properties of the synthesized organoselenium candidates were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and Glutathione Peroxidase (GPx)-like assays. Taken together, these NSAIDs-Se candidates could provide promising new lead derivatives for further potential Anticancer drug development.