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

Abstract

A series of organoselenium compounds based on the hybridization of nonsteroidal antiinflammatory drugs (NSAIDs) scaffolds and Se functionalities (-SeCN and -SeCF 3 ) 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 IC 50 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-SeCF 3 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.

Recent Advances in the Development of Direct Trifluoromethylselenolation Reagents and Methods

“…Some CF 3 Se-containing compounds have already exhibited properties that are amenable to potential anticancer drug development. [8] With more efforts devoted to exploring the altered properties of the trifluoromethylselenylated compounds, CF 3 Se-containing drugs will likely be developed in the near future. Last but not least, methodologies for the enantioselective synthesis of trifluoromethyselenolated compounds are underexplored and need to be developed.…”

“…Recently, Zhang and coworkers have developed the trifluoromethylselenolated nonsteroidal anti-inflammatory drugs (NSAIDs) that showed promising results on cancer cell viability, antioxidant activity and in docking studies, providing promising new lead compounds for future anti-cancer drug development. [8] Therefore, more and more research groups have shown a great interest in trifluoromethylselenolation chemistry. For the synthesis of trifluoromethylselenolated compounds, there have been two main approaches: indirect and direct introduction.…”

Catalytic Antioxidant Activity of Bis-Aniline-Derived Diselenides as GPx Mimics

“…In recent years, there has been an increasing interest in synthetic organoselenium compounds, mainly due to their properties as synthetic intermediates in organic transformations [ 1 , 2 , 3 ] and material sciences [ 4 , 5 ], as well as in medicinal chemistry [ 6 , 7 , 8 , 9 ]. These compounds have been recently described as good antioxidants [ 10 , 11 ], also presenting anti-inflammatory [ 12 , 13 ], antibacterial [ 14 ], antiviral [ 15 ], anticancer [ 16 , 17 , 18 , 19 ], anti-Alzheimer’s [ 20 , 21 , 22 , 23 ] and other activities [ 24 , 25 , 26 , 27 , 28 ]. Furthermore, in relation to the current pandemic of COVID-19, there are some interesting studies available that demonstrate the effectiveness of organoselenium compound (Ebselen) as an antiviral molecule, Figure 1 [ 29 , 30 , 31 ].…”

New Amides and Phosphoramidates Containing Selenium: Studies on Their Cytotoxicity and Antioxidant Activities in Breast Cancer

“…Accumulating evidence in the literature has illustrated that among the different selenated scaffolds, selenenocyanate [19,20] and diselenide [21][22][23] fragments are important pharmacophores that significantly suppress breast cancer. Furthermore, our research group has reported that selenocyanate and diselenide entities possess potent antitumor activity [24][25][26][27].…”