Design, Synthesis, Molecular Docking, and In Vitro Antiproliferative Evaluation of Quinoline–Pyranocoumarin Hybrids as Potent DNA Topoisomerase II Inhibitors

ABSTRACT A series of novel quinoline–pyranocoumarin hybrids incorporating quinoline and coumarin moieties were designed, synthesized, and evaluated as DNA topoisomerase II inhibitors. The key scaffold, 2‐amino‐5‐oxo‐4‐(quinolin‐4‐yl)‐4,5‐dihydropyrano[3,2‐c]chromene‐3‐carbonitrile, was obtained via a one‐pot reaction in 92% yield at room temperature. Ten derivatives ( 4a–4j ) were characterized by 1 H/ 13 C NMR and mass spectrometry. Docking studies against TOPO IIα (PDB ID: 5GWK) revealed compound 4b with the best binding affinity (−8.02 kcal/mol), outperforming doxorubicin. In vitro cytotoxicity on MCF‐7 and K562 cells showed lower IC 50 values for MCF‐7, and cell cycle analysis indicated G 2 /M arrest consistent with TOPO II inhibition.