Synthesis and quantum chemical studies of new 4-aminoquinazoline derivatives as Aurora A/B kinase inhibitors

Chem Biol Drug Des. 2013 Mar;81(3):399-407. doi: 10.1111/cbdd.12089. Epub 2012 Dec 26.

Abstract

Nine novel 4-aminoquinazoline derivatives were designed and synthesized. Biochemical and cellular analyses demonstrated that most of the derivatives exhibited a strong activity to inhibit Aurora A and B kinases and to suppress the proliferation of a panel of human tumor cell lines (U937, K562, A549, LoVo, and HT29). Quantum chemical studies were also carried out to determine the structural features of these compounds engaged in the inhibition of Aurora kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Aurora Kinases
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • HT29 Cells
  • Humans
  • K562 Cells
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / toxicity
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Quantum Theory*
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry*
  • Quinazolines / toxicity
  • Structure-Activity Relationship

Substances

  • 4-aminoquinazoline
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Aurora Kinases
  • Protein Serine-Threonine Kinases