Quinoline/Pyrido-Pyrimidine Derivatives as Tubulin Polymerization Inhibitors: Design, Synthesis, Computational, and Anticancer Evaluation.

Cancer prevails a substantial health threat, with breast and colon cancers being the second and third most recurrent worldwide. In recent decades, quinoline/pyrido[2,3-d]pyrimidin-4(3H)-one derivatives have procured attention as propitious anticancer agents. This study acquaint a series of such compounds synthesized and characterized using spectroscopic (1H NMR, 13C NMR, IR, MS) and computational (DFT) methods. Their tubulin polymerization inhibitory and antiproliferative activities were assessed against cancer cell lines MCF-7, MDA-MB-231, and HCT-116, accompanying cytotoxicity screening against normal HEK-293 cells, divulging selective anticancer potential. SAR study accentuated the role of methoxy-substituted phenyl and cycloheptane rings in escalating activity. Peculiarly, compound 4g (IC50 = 3.02 ± 0.63 μM against cell line MCF-7) exhibited profound tubulin inhibition and was additionally substantiated via molecular docking and dynamics simulations, ratifying its drug-like behavior.