Total synthesis of (+)-A83586C, (+)-kettapeptin and (+)-azinothricin: powerful new inhibitors of beta-catenin/TCF4- and E2F-mediated gene transcription.
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.
Hale
Karl J
KJ
The School of Chemistry and Chemical Engineering, and the Centre for Cancer Research and Cell Biology (CCRCB), Queen 's University Belfast, Stranmillis Road, Belfast, Northern Ireland, UK BT9 5AG. k.j.hale@qub.ac.uk
Manaviazar
Soraya
S
George
Jonathan
J
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047630:Depsipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D050684:E2F Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D047630:Depsipeptides; D050684:E2F Transcription Factors; D010455:Peptides; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; C512876:kettapeptin; C048098:azinothricin; C056791:A 83586C