Characterization of a novel barbituric acid and two thiobarbituric acid compounds for lung cancer treatment

Background/Aim: Previously, we reported the identification of a cytotoxic chemotype compound CC-I (1a), a derivative of thiobarbituric acid. We also reported the anticancer activity of a series of novel thio- and seleno-barbituric acid analogs. Materials and Methods: We herein evaluated the effect of 1a and its modified compounds on in vitro and in vivo lung cancer models. Results: The compounds 1b and 2a showed more potent cytotoxicity than 1a to lung cancer cells. Moreover, 1b did not have any cytotoxicity on normal cells, such as fibroblasts. In the human lung cancer A549 mouse tumor xenograft model, 1b and 2a showed more pronounced antitumor effects than 1a. In the A549 lung cancer cells, 1a induced cell death mainly via JNK and p38 MAPK activation. However, compound 1b and 2a induced lung cancer cell death mostly through JNK activation. Conclusion: The results suggest that 1b and 2a can be useful therapeutic agents for lung cancer.