New leukotriene B4 receptor antagonist: leucettamine A and related imidazole alkaloids from the marine sponge Leucetta microraphis.
Three new imidazole alkaloids, leucettamines A [1] and B [2] and leucettamidine [3], have been isolated from the Palauan sponge Leucetta microraphis. Their structures were established on the basis of extensive spectral analyses. Leucettamine A showed potent leukotriene B4 receptor binding activity (K(i) = 1.3 microM), while leucettamine B was essentially inactive (K(i) = 100 microM) and leucettamidine showed significant activity (K(i) = 5.3 microM). With leucettamine A identified as a pure LTB4 receptor antagonist, a new structure lead is presented to inflammation therapy.
Research and Development, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
G W
GW
Chan
S
S
Mong
M E
ME
Hemling
A J
AJ
Freyer
P H
PH
Offen
C W
CW
DeBrosse
H M
HM
Sarau
J W
JW
Westley
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004149:Dioxoles / Q000302:isolation & purification* / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D007093:Imidazoles / Q000302:isolation & purification* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D011161:Porifera / Q000737:chemistry*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018102:Receptors, Leukotriene B4; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D000470:Alkaloids; D004149:Dioxoles; D007093:Imidazoles; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; C000602884:leucettamine B; C080227:leucettamine A