2. Academic Validation
  3. Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents

Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents

  • Eur J Med Chem. 2016 Jan 27:108:364-373. doi: 10.1016/j.ejmech.2015.11.044.
Pan-Pan Ding 1,  Man Gao 1,  Bei-Bei Mao 1,  Sheng-Li Cao 2,  Cui-Huan Liu 1,  Chao-Rui Yang 1,  Zhong-Feng Li 1,  Ji Liao 3,  Hongchang Zhao 3,  Zheng Li 3,  Jing Li 3,  Hailong Wang 3,  Xingzhi Xu 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
  • 2 Department of Chemistry, Capital Normal University, Beijing, 100048, PR China. Electronic address: slcao@cnu.edu.cn.
  • 3 Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China.
  • 4 Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing, 100048, PR China. Electronic address: xingzhi_xu@mail.cnu.edu.cn.
PMID: 26703795 DOI: 10.1016/j.ejmech.2015.11.044
Abstract

A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 μM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint.

Keywords

Antiproliferative activity; Dithiocarbamate; G2/M arrest; Quinazolin-4(3H)-one; Spindle assembly checkpoint; Synthesis.

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