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

  • Eur J Med Chem. 2015 Apr 13:94:447-57. doi: 10.1016/j.ejmech.2015.02.058.
Ya-Juan Qin  1 ,  Yu-jing Li  1 ,  Ai-Qin Jiang  2 ,  Meng-Ru Yang  1 ,  Qi-Zhang Zhu  1 ,  Hong Dong  1 ,  Hai-Liang Zhu  3
Affiliations
  • 1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China.
  • 2. School of Medicine, Nanjing University, Nanjing 210093, PR China.
  • 3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China. Electronic address: [email protected].
PMID: 25828827 DOI: 10.1016/j.ejmech.2015.02.058
Abstract

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.

Keywords
Molecular docking; Pyrazoline; Tubulin polymerization inhibitors.