Exploring Anticancer Potential of Furopyrano[3,4‐b]Indole via Graphene Oxide‐Catalyzed Aqueous Synthesis.

A novel graphene oxide‐catalyzed two‐component cascade reaction in an aqueous medium has been developed to synthesize indole‐fused furopyran derivatives, overcoming significant challenges in aqueous organic reactions to advance eco‐friendly chemical processes. Density functional theory (DFT) studies were conducted to clarify the mechanism and to understand the role of temperature in forming our desired kinetic controlled product (KCP). Using a pharmacophore hybrid approach, a series of indole‐fused furopyran derivatives were designed and molecular docking was performed to assess their binding affinities toward target proteins in liver and breast cancer. The derivatives exhibited strong affinities, particularly towards the 4FA6 and 1U72 proteins, driven by hydrogen bonding interactions with specific amino acid residues. Ten best derivatives which showed strong binding affinities and favorable docking scores, were synthesized using the two‐component cascade reaction in an aqueous medium and tested for in vitro activity against liver and breast cancer cells. These derivatives showed notable antiproliferative activity against cancer cell lines, with promising IC50 values against breast and hepatocellular carcinoma, highlighting its potential as an anticancer drug candidate. The most potent compounds, 4d and 4f, demonstrated significant cytotoxicity against HepG2 and MCF7 cell lines, with IC50 values of 42.36 µM and 35.69 µM, respectively. To the best of our knowledge, the anti‐cancer activity of indole‐fused furopyran derivatives is being investigated for the first time for potential therapeutic development in combating these challenging diseases. [ABSTRACT FROM AUTHOR]