Synthesis and biological evaluation of novel 2-arylamino-3-(arylsulfonyl)quinoxalines as PI3Kα inhibitors

Eur J Med Chem. 2011 Nov;46(11):5540-8. doi: 10.1016/j.ejmech.2011.09.015. Epub 2011 Sep 17.

Abstract

A series of novel 2-arylamino-3-(arylsulfonyl)quinoxalines was synthesized through a newly developed approach. All synthesized target compounds were screened for their cytotoxicities against cancer cell lines including PC3, A549, HCT116, HL60 and KB. Representative compounds with favorable cytotoxicities were tested for their PI3Kα inhibitory activities. Among the synthesized target compounds, 17 (PI3Kα IC(50): 0.07 μM) displayed the most potent cellular activities (IC(50) values of 0.14 μM, 0.07 μM, 0.95 μM and 0.05 μM against PC3, A549, HCT116 and HL 60, respectively).

MeSH terms

  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic*
  • Class Ia Phosphatidylinositol 3-Kinase / chemistry
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Conformation
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Quinoxalines
  • Class Ia Phosphatidylinositol 3-Kinase