Pyrazino[1,2-a]indole-1,4-diones, simple analogues of gliotoxin, as selective inhibitors of geranylgeranyltransferase I

Bioorg Med Chem Lett. 2003 Nov 3;13(21):3661-3. doi: 10.1016/j.bmcl.2003.08.022.

Abstract

Some pyrazino[1,2-a]indole-1,4-diones, structurally simplified analogues of the natural mycotoxin gliotoxin, have been synthesised and investigated as inhibitors of prenyltransferases; one compound, 3-acetylthio-9-methoxy-2-methyl-2,3-dihydropyrazino[1,2-a]indole-1,4-dione 10 shows slightly greater selectivity (8-fold) for geranylgeranyltransferase type I (GGTase I) than gliotoxin itself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Farnesyltranstransferase
  • Genes, ras / genetics
  • Gliotoxin / analogs & derivatives*
  • Gliotoxin / pharmacology*
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Pyrazines / chemical synthesis*
  • Pyrazines / pharmacology*
  • Recombinant Proteins / chemical synthesis
  • Recombinant Proteins / pharmacology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Indoles
  • Pyrazines
  • Recombinant Proteins
  • Gliotoxin
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Farnesyltranstransferase