2. Academic Validation
  3. Optimization of substituted cinnamic acyl sulfonamide derivatives as tubulin polymerization inhibitors with anticancer activity

Optimization of substituted cinnamic acyl sulfonamide derivatives as tubulin polymerization inhibitors with anticancer activity

  • Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3634-3638. doi: 10.1016/j.bmcl.2018.10.037.
Yin Luo 1,  Yang Zhou 2,  Yanhua Song 3,  Guo Chen 4,  Yu-Xiang Wang 5,  Ye Tian 5,  Wei-Wei Fan 5,  Yu-Shun Yang 5,  Tao Cheng 6,  Hai-Liang Zhu 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: luoyin147@163.com.
  • 2 Cixi Institute of BioMedical Engineering, Ningbo Institute of Industrial Technology, CAS, Ningbo 315201, People's Republic of China.
  • 3 Tianjin 4th Centre Hospital, Tianjin 300140, People's Republic of China.
  • 4 Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
  • 6 Pharmaron Ningbo Co., Ltd., Ningbo 315366,People's Republic of China.
  • 7 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
PMID: 30389289 DOI: 10.1016/j.bmcl.2018.10.037
Abstract

A new series of novel cinnamic acyl sulfonamide derivatives were designed and synthesized and evaluated their anti-tubulin polymerization activities and Anticancer activities. One of these compounds, compound 5a with a benzdioxan group, was observed to be an excellent tubulin inhibitor (IC50 = 0.88 µM) and display the best antiproliferative activity against MCF-7 with an IC50 value of 0.17 μg/mL. Docking simulation was performed to insert compound 5a 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 anti-tubulin polymerization activity.

Keywords

Anti-tubulin polymerization; Antiproliferative activity; Cinnamic acid; Molecular docking; Sulfonamide.

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