Design, synthesis and biological evaluation of novel pyrazoline-containing derivatives as potential tubulin assembling inhibitors

• DOI: 10.1016/j.ejmech.2015.02.058
• Publication Date: 2015-03-03T13:24:27Z
• Authors: Ya-Juan Qin; Yu-jing Li; Ai-Qin Jiang; Meng-Ru Yang; Qi-Zhang Zhu; Hong Dong; Hai-Liang Zhu
• Keywords: Pyrazoline; Docking (animal); IC50; Lead compound

A series of novel pyrazoline-containing derivatives (15-47) has been designed, synthesized and evaluated for their biological activities. Among them, compound 18 displayed the most potent antiproliferative activity against A549, MCF-7 and HepG-2 cells line (IC50 = 0.07 μM, 0.05 μM, 0.03 μM, respectively) and the tubulin polymerization inhibitory activity (IC50 = 1.88 μM), being comparable to CA-4. Furthermore, we also tested that compound 18 was a potent inducer of apoptosis in HepG-2 cells and it had cellular effects typical for microtubule interacting agents, causing accumulation of cells in the G2/M phase of the cell cycle. These studies, along with molecular docking, provided a new molecular scaffold for the further development of antitumor agents that target tubulin.