Affiliation:
1. Laboratory of Applied Chemistry: Heterocycles Lipids and Polymers Faculty of Sciences of Sfax University of Sfax BP 802 3000 Sfax Tunisia
2. Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax Sidi Mansour Road Km 6, BP 1177, 3018 Sfax Tunisia
3. Laboratoire LINC UR 481 Pôle de Chimie Médicinale Université Franche-Comté, UFR Santé 19, Rue Ambroise Paré F-25000 Besançon France.
4. Laboratory of Medicinal Chemistry (IQOG, CSIC) C/Juan de la Cierva 3 28006 Madrid Spain
5. Center for Biomedical Network Research on Rare Diseases (CIBERER) CIBER, ISCIII 28006 Madrid Spain
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.
Funder
Conseil régional de Bourgogne-Franche-Comté