Synthesis and in vitro evaluation of new wortmannin esters: potent inhibitors of phosphatidylinositol 3-kinase

J Med Chem. 1996 Dec 6;39(25):5021-4. doi: 10.1021/jm960283z.


New C-11 esters of the fermentation product wortmannin have been synthesized, with some of them further derivatized at C-17. The new esters show greater inhibition of isolated phosphatidylinositol 3-kinase and increased cell cytotoxicity in a rapidly proliferating leukemia cell line, when compared to wortmannin. Reduction of the C-17 ketone caused a slight increase in activity, while acylation of this new alcohol caused severe loss of activity. With their increased activity, the new C-11 esters may be good candidates to explore the in vivo antitumor effects of phosphatidylinositol 3-kinase inhibitors.

MeSH terms

  • Androstadienes / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Esters
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Tumor Cells, Cultured
  • Wortmannin


  • Androstadienes
  • Enzyme Inhibitors
  • Esters
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Wortmannin