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

Abstract

AbstractHerein 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.