Synthesis and Anti-Tumor Effects of Novel Pomalidomide Derivatives Containing Urea Moieties

In order to explore novel immunomodulatory agents as anti-tumor drugs, we designed and synthesized a series of new pomalidomide derivatives containing urea moieties. Interestingly, in vitro biological experiments performed in several cancer cell lines showed that some of them displayed potent anti-tumor ability. These novel compounds5a–5eand6a–6edemonstrated the best cell growth inhibitive activity in human breast cancer cell lines MCF-7, but weaker inhibitive activity in human hepatocellular carcinoma cell lines Huh7. Moreover, compound5dhad the most powerful effects in this study, with an IC50value of 20.2 μM in MCF-7. Further study indicated that compound5dcould inhibit cell growth and induce cell death in a concentration-dependent manner. Besides, compound5dincreased cellular ROS levels and induced DNA damage, thereby potentially leading to cell apoptosis. These observations suggest that the novel pomalidomide derivatives containing urea moieties may be worth further investigation to generate potential anti-tumor drugs.Keywords:pomalidomide derivatives;urea moieties;immunomodulatory;anti-tumor effects