New leukotriene B4 receptor antagonist: leucettamine A and related imidazole alkaloids from the marine sponge Leucetta microraphis

J Nat Prod. 1993 Jan;56(1):116-21.

Abstract

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.

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Cells, Cultured
  • Dioxoles / isolation & purification*
  • Dioxoles / pharmacology
  • Gas Chromatography-Mass Spectrometry
  • Imidazoles / isolation & purification*
  • Imidazoles / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Porifera / chemistry*
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Leukotriene B4
  • Spectrometry, Mass, Fast Atom Bombardment
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Dioxoles
  • Imidazoles
  • Receptors, Immunologic
  • Receptors, Leukotriene B4
  • leucettamine B
  • leucettamine A