Synthesis, molecular docking and pharmacological studies of novel quinoline derivative as anticancer agent that targets topoisomerase IIB

Topoisomerase plays a critical role in refining the DNA strands during the replication process by reliving the topological stress. Aberrant over expression of TOPO enzymes have been observed in many cancer cells. Topoisomerase has been an attractive target to fight against cancer cells due to its critical role in refining the DNA strands. Inhibition of topoisomerase leads to double strand break, persistent accumulation of these double strand breaks are very lethal and eventually leads to apoptosis. Compound 4l was very potent in inducing cell death in screened breast cancer cells, 4l abrogates proliferation of MDA-MB-231 and MBA-MB-468 cells with IC50 18.94 and 22.68 µM respectively. Uptake of propidium iodide by cells in Hoechst and Pi double staining displays induction of apoptosis by 4l in both breast cancer cells. Molecular docking of 4l with the Topoisomerase enzyme reveals strong interactions with -8.39 K Cal/mol and Molecular dynamics simulations unveils strong hydrophobic interactions with Topoisomerase.