Synthesis and antitumor activity evaluation of coumarin Mannich base derivatives

Abstract Twenty‐one new coumarin Mannich base derivatives ( 11a‐u ) were synthesized, which exhibited antiproliferation activities in HepG2 (liver cancer), A549 (lung cancer), MCF‐7 (breast cancer), and HT‐29 (colon cancer). Most of the target compounds showed the most potent activity against HepG2 cells compared with other cancer cells, compound 11g showed the strongest antiproliferative activity (2.10 μM) against HepG2, even superior to the positive control drug 5‐FU(5.49 μM). The nitric oxide (NO) release of all compounds in HepG2 cells was determined, of which compound 11g showed high levels of NO release (10.8 μM). Notably, the solubility of compound 11g increased 13‐fold compared with the lead 8 . The preliminary cytotoxicity studies suggest that 11g had little effect on LO2 cells(normal liver cells, >50 μM). The effect of compound 11g on the apoptosis of HepG2 cells was also studied, and the results showed that the induction effect of compound 11g on apoptosis is a concentration‐dependent manner. Our results indicate that compound 11g might be a promising lead for further studies.