Viridin analogs derived from steroidal building blocks

Bioorg Med Chem Lett. 2012 Nov 15;22(22):6919-22. doi: 10.1016/j.bmcl.2012.09.015. Epub 2012 Sep 13.

Abstract

Naturally occurring furanosteroids such as viridin and wortmannin have long been known as potent inhibitors of the lipid kinase PI-3K. We have been interested in directly accessing analogs of these complex natural products from abundant steroid feedstock materials. In this communication, we describe the synthesis of viridin/wortmannin hybrid molecules from readily available building blocks that function as PI-3K inhibitors and maintain their electrophilic properties. The compounds also show anti-proliferative effects against a breast cancer line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / chemistry
  • Androstenes / chemical synthesis
  • Androstenes / chemistry*
  • Androstenes / toxicity
  • Bacteriocins / chemical synthesis
  • Bacteriocins / chemistry*
  • Bacteriocins / toxicity
  • Binding Sites
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Female
  • Humans
  • MCF-7 Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / toxicity
  • Protein Structure, Tertiary
  • Steroids / chemistry*
  • Wortmannin

Substances

  • Androstadienes
  • Androstenes
  • Bacteriocins
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Steroids
  • viridin
  • Wortmannin