Exiguamine A, an indoleamine-2,3-dioxygenase (IDO) inhibitor isolated from the marine sponge Neopetrosia exigua.
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.
Brastianos
Harry C
HC
Department of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
Vottero
Eduardo
E
Patrick
Brian O
BO
Van Soest
Rob
R
Matainaho
Teatulohi
T
Mauk
A Grant
AG
Andersen
Raymond J
RJ
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009792:Oceans and Seas; D011161:Porifera / Q000737:chemistry* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry* / Q000302:isolation & purification*
D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D013141:Spiro Compounds; C516830:exiguamine A