Exiguamine A, an indoleamine-2,3-dioxygenase (IDO) inhibitor isolated from the marine sponge Neopetrosia exigua

J Am Chem Soc. 2006 Dec 20;128(50):16046-7. doi: 10.1021/ja067211+.

Abstract

Exiguamine A (1), a hexacyclic alkaloid with an unprecedented skeleton, has been isolated from the marine sponge Neopetrosia exigua collected in Papua New Guinea. The structure of exiguamine A (1) was elucidated by a combination of spectroscopic analysis and single-crystal X-ray diffraction analysis. Exiguamine A (1) has a Ki of 210 nM for inhibition of indoleamine-2,3-dioxygenase (IDO) in vitro, making it one of the most potent IDO inhibitors known to date. A putative biogenesis for the new exiguamine skeleton starts from DOPA, tryptophan, and N,N-dimethylhydantoin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / metabolism
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Indoles / chemistry*
  • Indoles / isolation & purification*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Oceans and Seas
  • Porifera / chemistry*
  • Porifera / metabolism
  • Spiro Compounds / chemistry*
  • Spiro Compounds / isolation & purification*

Substances

  • Enzyme Inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Indoles
  • Spiro Compounds
  • exiguamine A