Synthesis and Biological Evaluation of New Benzochromenopyrimidines for the Therapy of Colon and Lung Cancer

Herein we report the synthesis of ten newly substituted 3-phenyl-5-aryl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidin-4,6,11-triones ("benzochromenopyrimidines") in a one-step reaction, by reacting ethyl 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-3-carboxylates with aniline, and triethyl orthoformate, under acidic catalyst and solvent-free conditions. These benzochromenopyrimidines were submitted to biological evaluation for in vitro anti-cancer activity, several derivatives showing higher activity than commonly used chemotherapeutic agents such as oxaliplatin, 5-fluorouracil, and paclitaxel. In particular, the 5-(2-Methoxyphenyl)-3-phenyl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione was identified as the most potent inhibitor among all the new ligands, showing significant cytotoxic activity against all the cancer cell lines tested [human colon cancer cell lines, LoVo and HCT-116; human lung cancer cells (A549 line)], as evidenced by the significant decrease in IC50 values, while maintaining low cytotoxicity against normal cells. These promising results suggest that this compound deserves further investigation as a potential hit compound for the development of a selective anticancer drug in cancer therapy. From benzochromenopyrimidines 3 a-j prepared in a one-pot reaction, compound 3 b was identified as the most potent inhibitor among all the new ligands, showing significant cytotoxic activity against all the cancer cell lines tested [human colon cancer cell lines, LoVo and HCT-116; human lung cancer cells (A549 line)], as evidenced by the significant decrease in IC50 values, while maintaining low cytotoxicity against normal cells.image