2. Academic Validation
  3. Synthesis, biological evaluation and 3D-QSAR studies of novel 5-phenyl-1H-pyrazol cinnamamide derivatives as novel antitubulin agents

Synthesis, biological evaluation and 3D-QSAR studies of novel 5-phenyl-1H-pyrazol cinnamamide derivatives as novel antitubulin agents

  • Eur J Med Chem. 2015 Mar 26:93:291-9. doi: 10.1016/j.ejmech.2015.02.018.
Shu-Fu Wang 1,  Yong Yin 1,  Ya-Liang Zhang 1,  Shan-Wei Mi 1,  Meng-Yue Zhao 1,  Peng-Cheng Lv 1,  Bao-Zhong Wang 1,  Hai-Liang Zhu 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
PMID: 25703297 DOI: 10.1016/j.ejmech.2015.02.018
Abstract

A series of novel 5-phenyl-1H-pyrazol derivatives (5a-5x) containing cinnamamide moiety were synthesized and their biological activities as potential tubulin polymerization inhibitors were evaluated. Among them, compound 5j exhibited the most potent inhibitory activity with an IC50 value of 1.02 μM for tubulin, which was superior to that of Colchicine (IC50 = 1.34 μM). Docking simulation was performed to insert compound 5j into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin inhibitory activity.

Keywords

3D-QSAR; Antitubulin agent; Cinnamamide; Molecular docking; Pyrazole.

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