2. Academic Validation
  3. Molecular diversity of trimethoxyphenyl-1,2,3-triazole hybrids as novel colchicine site tubulin polymerization inhibitors

Molecular diversity of trimethoxyphenyl-1,2,3-triazole hybrids as novel colchicine site tubulin polymerization inhibitors

  • Eur J Med Chem. 2019 Mar 1:165:309-322. doi: 10.1016/j.ejmech.2019.01.033.
Dong-Jun Fu 1,  Ping Li 2,  Bo-Wen Wu 2,  Xin-Xin Cui 2,  Cheng-Bin Zhao 3,  Sai-Yang Zhang 4
Affiliations

Affiliations

  • 1 School of Basic Medical Science, Zhengzhou University, Zhengzhou, 450001, China; School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China.
  • 2 School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China.
  • 3 The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 4 School of Basic Medical Science, Zhengzhou University, Zhengzhou, 450001, China; The Academy of Medical Science, Zhengzhou University, Zhengzhou, 450001, China; Henan Institutes of Advanced Technology, Zhengzhou University, Zhengzhou, 450001, China; School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: saiyangz@zzu.edu.cn.
PMID: 30690300 DOI: 10.1016/j.ejmech.2019.01.033
Abstract

Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three Cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better antiproliferative activity results with IC50 values from 0.13 μM to 1.74 μM than Anticancer drug colchicine. Compound 19c could inhibit MGC803 cell growth and colony formation, induce G2/M phase arrest by down expression of CDK1, and promote Apoptosis by regulating DR5 and Bcl-2 Family. Moreover, 19c strongly inhibited tubulin polymerization by interacting with the colchicine site.

Keywords

Apoptosis; Cell cycle; Colchicine site tubulin inhibitor; Coumarin; Trimethoxyphenyl-1,2,3-triazole.

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