Synthesis and antitumor activities of quaternary carbon-containing selenolactones

The cytotoxicity of α-exo-methylene-lactones has been extensively studied. However, further study of the α-exo-methylene-lactones for anticancer application was hampered primarily by its poor selectivity and solubility. In the present work, a series of α-exo-methylene-selenolactone derivatives bearing amine substituent, selenium functionality and quaternary carbon center were synthesized and evaluated for their anticancer activities. The most potent compound, 2d, was about 9-fold more selective for cancer cells than normal cells. Moreover, 2d significantly inhibited tumor growth in mouse xenograft model and had no observable toxic effect.