Design, Synthesis, and Biological Evaluation of Novel Selenium (Se-NSAID) Molecules as Anticancer Agents

The
synthesis and anticancer evaluation of novel selenium-nonsteroidal
anti-inflammatory drug (Se-NSAID) hybrid molecules are reported. The
Se-aspirin analogue 8 was identified as the most effective
agent in reducing the viability of different cancer cell lines, particularly
colorectal cancer (CRC) cells, was more selective toward cancer cells
than normal cells, and was >10 times more potent than 5-FU, the
current
therapy for CRC. Compound 8 inhibits CRC growth via the
inhibition of the cell cycle in G1 and G2/M phases and reduces the
cell cycle markers like cyclin E1 and B1 in a dose dependent manner;
the inhibition of the cell cycle may be dependent on the ability of 8 to induce p21 expression. Furthermore, 8 induces
apoptosis by activating caspase 3/7 and PARP cleavage, and its longer
exposure causes increase in intracellular ROS levels in CRC cells.
Taken together, 8 has the potential to be developed further
as a chemotherapeutic agent for CRC.