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

Jin Cai, Lili Li, Kwon Ho Hong, Xiaoqing Wu, Junqing Chen, Peng Wang, Meng Cao, Xi Zong, Min Ji

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)5813-5823
Number of pages11
JournalBioorganic and Medicinal Chemistry
Issue number21
StatePublished - Nov 1 2014

Bibliographical note

Funding Information:
This work is supported by The Fundamental Research Funds for the Central Universities ( 2242014R30019 ), Technology Supporting Program of Jiangsu province ( BE2012657 ), and National Basin Research Program of China (No. 2011CB933503 ). We thank the Minnesota Supercomputing Institute for their support for our molecular modeling study.

Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.


  • Antiproliferative activity
  • Aurora kinase
  • Cancer cell
  • Docking simulation
  • Quinazolines
  • ZM447439


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