Benzo[ f ]chromene Derivatives as Cytotoxic Agents: Design, Synthesis, Molecular Docking, and ADMET

High Resolution Image Download MS PowerPoint Slide A series of novel benzo[ f ]chromene derivatives, 4–14, were successfully synthesized and structurally characterized using spectroscopic techniques, including IR, 1 H-NMR, and 13 C-NMR. The antiproliferative activities of selected compounds were evaluated against three human cancer cell lines─ HepG-2 (hepatocellular carcinoma), HCT-116 (colorectal carcinoma), and MCF-7 (breast cancer)─using the MTT assay. Cytotoxic effects were compared to standard anticancer agents 5-Fluorouracil and Doxorubicin. Among the tested compounds, 7, 9, and 12 exhibited superior cytotoxicity across all three cell lines, outperforming the reference drugs. Structure–activity relationship (SAR) analysis suggested that fused heterocyclic moieties at the 2,3-position significantly enhanced anticancer activity. Furthermore, in silico molecular docking studies targeting the EGFR tyrosine kinase domain (PDB ID: 4HJO ) demonstrated that compound 12 and the reference ligand AQ4 formed stable interactions with key active-site residues, suggesting a potential mechanism of action through EGFR inhibition that warrants further experimental validation. These findings suggest that the synthesized benzo[ f ]chromene derivatives, particularly benzo[ f ]chromenopyrimidine derivative 12, represent promising lead candidates for further development pending validation of their proposed mechanism of action, warranting future biochemical and cellular validation.