Design, Synthesis and Pharmacological Evaluation of 4-Hydroxycoumarin Derivatives as Antiproliferative Agents.

A series of novel 4-hydroxycoumarin based acryloylcyanohydrazone derivatives were synthesized and evaluated for in vitro antiproliferative activity against different cancer cell lines (A-549, HeLa, SK-N-SH, and MCF-7) by MTT assay method. All the test compounds (8 a-m) were exhibited excellent antiproliferative activity (IC50 values ranging between 8.20 to 27.39 mu M) against all the tested cancer cell lines. Pharmacological studies like cell cycle progression arrest and tubulin polymerisation inhibition studies were performed for the most potent compound 8 j. Further these studies were confirmed that the compound 8 j induced the cell cycle arrest at G2/M phase and tubulin polymerisation was inhibited with IC50=11.03 mu M. Molecular docking simulation for the compound 8 j also revealed that, it has strong binding interactions towards tubulin protein. This in silico target validation suggested the tubulin is the target for the designed potent compound 8 j.