Abstract:

The highly dynamic microtubules of the mitotic spindle are well-established biochemical targets for anticancer drugs such as paclitaxel, vinblastine, and vincristine. However, a significant clinical challenge is the emergence of resistance to these agents, highlighting the urgent need for novel anticancer compounds that target tubulin. In this study, a panel of chloroquinoline derivatives was synthesized and characterized using ¹H NMR, FTIR, and mass spectrometry. The antiproliferative activity of these compounds was evaluated against the breast cancer cell lines MCF-7 and MDA-MB-231. Of the tested molecules, CQ-9 and CQ-14 displayed IC₅₀ values of 5.6 μM and 4.55 μM, respectively, against MDA-MB-231 cells, while CQ-9 exhibited an IC₅₀ of 13.05 μM for MCF-7 cells. All compounds (CQ-1 to CQ-14) were subjected to molecular docking studies using the Schrödinger software suite to investigate their interactions with tubulin. The resulting ligand-protein complexes were analyzed for binding energies, and the most stable complexes were selected for further molecular dynamics simulations. Tubulin was chosen as a likely target owing to the structural similarity of the reported compounds to quinolinyl and other herteroaryl chalcones that have shown to inhibit Tubulin by binding to Colchicine binding site. Hence , we used specific crystal structure of tubulin (PDB id: 1SA0) co-complexed with Colchicine for our molecular docking studies.