2. Academic Validation
  3. Bioactive heterocycles containing a 3,4,5-trimethoxyphenyl fragment exerting potent antiproliferative activity through microtubule destabilization

Bioactive heterocycles containing a 3,4,5-trimethoxyphenyl fragment exerting potent antiproliferative activity through microtubule destabilization

  • Eur J Med Chem. 2018 Sep 5:157:50-61. doi: 10.1016/j.ejmech.2018.07.060.
Dong-Jun Fu 1,  Jia-Jia Yang 1,  Ping Li 1,  Yu-Hui Hou 1,  Sheng-Nan Huang 1,  Matthew Alexander Tippin 2,  Victor Pham 2,  Liankun Song 2,  Xiaolin Zi 2,  Wei-Li Xue 3,  Li-Rong Zhang 4,  Sai-Yang Zhang 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China.
  • 2 Department of Urology, University of California, Irvine, Orange, CA 92868, USA.
  • 3 The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China.
  • 4 School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, China. Electronic address: Zhnaglirongzzu@126.com.
  • 5 School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, China. Electronic address: celeron16@163.com.
PMID: 30075402 DOI: 10.1016/j.ejmech.2018.07.060
Abstract

Novel bioactive heterocycles containing a 3,4,5-trimethoxyphenyl fragment as antiproliferative agents by targeting tubulin were synthesized and their preliminary structure activity relationships (SARs) were explored. Among all these chemical agents, 2-(Benzo[d]oxazol-2-ylthio)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (4d) exhibited the potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.45 μM by induction of G2/M pahse arrest and cell Apoptosis. In addition, 4d could change the membrane potential (ΔΨ) of the mitochondria against MGC-803 cells. Importantly, 4d acted as a novel tubulin polymerization inhibitor binding to colchicine site with an IC50 value of 3.35 μM.

Keywords

3,4,5-Trimethoxyphenyl fragment; Apoptosis; Colchicine site; G2/M; Tubulin polymerization; ΔΨ.

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