2. Academic Validation
  3. Discovery of 4-aminoquinazoline--urea derivatives as Aurora kinase inhibitors with antiproliferative activity

Discovery of 4-aminoquinazoline--urea derivatives as Aurora kinase inhibitors with antiproliferative activity

  • Bioorg Med Chem. 2014 Nov 1;22(21):5813-23. doi: 10.1016/j.bmc.2014.09.029.
Jin Cai 1,  Lili Li 1,  Kwon Ho Hong 2,  Xiaoqing Wu 3,  Junqing Chen 1,  Peng Wang 4,  Meng Cao 4,  Xi Zong 1,  Min Ji 5
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
  • 2 Department of Medicinal Chemistry and The Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, MN 55414, USA.
  • 3 Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
  • 4 School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China.
  • 5 School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China; School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China. Electronic address: jimin@seu.edu.cn.
PMID: 25270403 DOI: 10.1016/j.bmc.2014.09.029
Abstract

Two series of 20 novel 4-aminoquinazoline-urea derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activity against six human Cancer cell lines (K562, U937, A549, NCI-H661, HT29 and LoVo) using the MTT-based assay. Most compounds showed significant antiproliferative activities against four solid tumor cell lines, but no or poor activities against two leukemia cell lines. Furthermore, the target compounds were screened for Aurora A/B kinases inhibitory activity. Among them, 7c, 7d, 8c, and 8d are more potent against Aurora A kinase than ZM447439. Docking study of compounds 7d and ZM447439 revealed that they bound strongly to the ATP-binding sites of Aurora A and B. Thus, they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting Aurora kinases.

Keywords

Antiproliferative activity; Aurora kinase; Cancer cell; Docking simulation; Quinazolines; ZM447439.

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