Discovery of potent cell migration inhibitors through total synthesis: lessons from structure-activity studies of (+)-migrastatin

J Am Chem Soc. 2004 Feb 4;126(4):1038-40. doi: 10.1021/ja039714a.

Abstract

Synthesis of highly active migrastatin-based tumor migration cell inhibitors has been accomplished. Our flexible and concise total synthesis of migrastatin has allowed us to explore otherwise inaccessible migrastatin-derived structural motifs. This effort has resulted in the discovery of analogues with tumor cell migration inhibitory activity 3 orders of magnitude higher than that of the natural product.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Drug Design
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Humans
  • Lactones / chemical synthesis*
  • Lactones / chemistry*
  • Lactones / pharmacology
  • Macrolides*
  • Mice
  • Piperidones / chemical synthesis*
  • Piperidones / chemistry*
  • Piperidones / pharmacology
  • Structure-Activity Relationship

Substances

  • Angiogenesis Inhibitors
  • Lactones
  • Macrolides
  • Piperidones
  • migrastatin