Total synthesis of (+)-A83586C, (+)-kettapeptin and (+)-azinothricin: powerful new inhibitors of beta-catenin/TCF4- and E2F-mediated gene transcription

Chem Commun (Camb). 2010 Jun 21;46(23):4021-42. doi: 10.1039/c000603c. Epub 2010 Apr 19.

Abstract

Herein we describe our asymmetric total syntheses of (+)-A83586C, (+)-kettapeptin and (+)-azinothricin. We also demonstrate that molecules of this class powerfully inhibit beta-catenin/TCF4- and E2F-mediated gene transcription within malignant human colon cancer cells at low drug concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / antagonists & inhibitors*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Depsipeptides / chemical synthesis
  • Depsipeptides / pharmacology*
  • E2F Transcription Factors / genetics*
  • E2F Transcription Factors / metabolism
  • Humans
  • Peptides / chemical synthesis
  • Peptides / pharmacology*
  • Transcription Factor 4
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects*
  • beta Catenin / antagonists & inhibitors*
  • beta Catenin / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Depsipeptides
  • E2F Transcription Factors
  • Peptides
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • beta Catenin
  • kettapeptin
  • azinothricin
  • A 83586C