Synthesis and Antitumor Evaluation of a Novel Class of Chalcone Mannich Base Derivatives.

A novel class of chalcone Mannich base derivatives I1-9 and II1-11 was synthesized, which exhibited significant antiproliferation activities in five different cancer cells. The activities of most compounds were superior to those of the positive control drug 5-FU. Moreover, compared with the intermediate chalcone, their water solubility was also significantly enhanced. Among them, the most prospective compound I4 (IC50 = 3.09-5.08 μM for the tested cancer cells) can effectively inhibit the proliferation of A549/DDP cells (IC50 = 4.69 μM). Further mechanistic studies revealed that it can induce apoptosis of A549 and A549/DDP cells by arresting the G2/M phase of the cell cycle. Although the selectivity of compound I4 between tumor cells and normal cells was not obvious, it might be a promising lead compound for lung cancer and is worthy of further investigation.