Synthesis, Anticancer Activity and Molecular Docking of Quinazolinedione derivatives

Abstract

A new series of quinazolinidione–amide derivatives (B1–B5) was synthesized through a two-step procedure involving palladium-catalyzed cyclization followed by amide coupling with substituted anilines. The structures of the synthesized compounds were confirmed using spectroscopic techniques such as ¹H NMR and LCMS, and their purity was validated through elemental analysis. The anticancer activity of the compounds was evaluated in vitro against the MCF-7 human breast cancer cell line using the Sulforhodamine B (SRB) assay. Among the tested derivatives, B3 and B5 exhibited significant cytotoxicity, with IC₅₀ values of 9.1 µg/mL and 10.2 µg/mL, respectively, compared to standard drugs Doxorubicin and Erlotinib. Molecular docking studies were conducted using AutoDock Vina to predict protein–ligand interactions with the target receptor (PDB ID: 1M17). The results revealed strong binding affinities for all synthesized compounds, with B5 displaying the highest docking score (–9.9 kcal/mol). Consistent hydrophobic and hydrogen-bonding interactions were observed across the series. Overall, the integrated synthetic, biological, and computational findings suggest that compounds B3 and B5 are promising candidates for further development as anticancer agents.