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

A novel class of chalcone Mannich base derivatives I_1-9 and II_1-11 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.