Discovery of new azaindole-based PI3Kα inhibitors: apoptotic and antiangiogenic effect on cancer cells

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7212-5. doi: 10.1016/j.bmcl.2010.10.108. Epub 2010 Oct 26.

Abstract

Phosphatidylinositol-3-kinase alpha (PI3Kα) is an important target in cancer due to the deregulation of the PI3K/AKT signaling pathway in many tumors. In this study, we designed [3,5-d]-7-azaindole analogs as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3,5-positions of azaindole, we developed the SAR (Structure-activity relationship) and identified a series of potent PI3Kα inhibitors. Representative azaindole derivatives showed activity in a cellular proliferation and apoptosis assays. Moreover, B3 exhibited strong antiangiogenic effects on cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / therapeutic use
  • Apoptosis*
  • Breast Neoplasms / drug therapy
  • Cell Line, Tumor
  • Cell Movement
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / therapeutic use
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / therapeutic use

Substances

  • 7-azaindole dimer
  • Angiogenesis Inhibitors
  • Enzyme Inhibitors
  • Indoles
  • Phosphoinositide-3 Kinase Inhibitors
  • Sulfonamides