Planta Med 2004; 70(10): 883-886
DOI: 10.1055/s-2004-832610
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Prenylated Indole Alkaloids from Flustra foliacea with Subtype Specific Binding on NAChRs

Lars Peters1 , Anthony D. Wright1 , Stefan Kehraus1 , Daniela Gündisch2 , M. C. Tilotta2 , Gabriele M. König1
  • 1Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany
  • 2Institute for Pharmaceutical Chemistry, University of Bonn, 53115 Bonn, Germany
Further Information

Publication History

Received: February 23, 2004

Accepted: July 26, 2004

Publication Date:
18 October 2004 (online)

Abstract

Several brominated indole alkaloids and a diterpene (1 - 7) were isolated from the dichloromethane extract of the North Sea Bryozoan Flustra foliacea. Alkaloid 4 is a new natural product, whose structure was elucidated by interpretation of spectroscopic data (NMR, mass, UV, and IR). All compounds were tested for their in vitro affinity towards the α4ß2* and α7* subtype of the neuronal nicotinic acetylcholine receptor (nAChR) using radioligand binding assays. Deformylflustrabromine (3) and deformylflustrabromine B (4) were shown to have affinities in the lower micromolar range for nAChRs, differing in their subtype preference.

References

  • 1 Lindstrom J. Neuronal nicotinic acetylcholine receptors.  Ion Channels. 1996;  4 377-450
  • 2 Clementi F, Fornasari D, Gotti C. Neuronal nicotinic receptors, important new players in brain functions.  Eur J Pharmacol. 2000;  393 3-10
  • 3 Lena C, Changeux J P. Pathological mutations of nicotinic receptors and nicotine-based therapies for brain disorders.  Curr Opin Neurobiol. 1997;  7 674-82
  • 4 Nordberg A. PET studies and cholinergic therapy in Alzheimer’s disease.  Rev Neurol (Paris). 1999;  155 53-63
  • 5 Freedman R, Adams C E, Leonard S. The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia.  J Chem Neuroanat. 2000;  20 299-306
  • 6 Peters L, König G M, Terlau H, Wright A D. Four new bromotryptamine derivatives from the marine Bryozoan Flustra foliacea .  J Nat Prod. 2002;  65 1633-7
  • 7 Sjöblom T, Bohlin L, Christophersen C. Studies of Swedish marine organisms. II. Muscle-relaxant alkaloids from the marine Bryozoan Flustra foliacea .  Acta Pharm Suec. 1983;  20 415-9
  • 8 Spande T F, Edwards M W, Pannell L K, Daly J W, Erspamer V, Melchiorri P. Pseudophrynamine A: an unusual prenylated pyrrolo[2,3-b]indole ester from an Australian frog, Pseudophryne coriacea (Myobatrachidae).  J Org Chem. 1988;  53 1222-6
  • 9 Alkondon M, Pereira E FR, Cortes W S, Maelicke A, Albuquerque E. Choline is a selective agonist of alpha 7 nicotinic acetylcholine receptors in the rat brain neurons.  Eur J Neurosci. 1997;  9 2734-42
  • 10 Wright A D, König G M, Angerhofer C K, Greenidge P, Linden A, Desqueyroux-Faundez R J. Antimalarial activity: the search for marine-derived natural products with selective antimalarial activity.  J Nat Prod. 1996;  59 710-6
  • 11 Gündisch D, London E D, Terry P, Hill G R, Mukhin G. High affinity binding of [3 H]epibatidine to rat brain membranes.  NeuroReport. 1999;  10 1631-6
  • 12 Gündisch D, Harms K, Schwarz S, Seitz G, Stubbs M T, Wegge T. Synthesis and evaluation of diazine containing bioisosteres of (-)-ferruginine as ligands for nicotinic acetylcholine receptors.  Bioorg Med Chem. 2001;  9 2683-91
  • 13 Davies A RL, Hardick D J, Blagbrough I S, Potter B VL, Wolstenholme A J, Wonnacott S. Characterisation of the binding of [3 H]-methyllycaconitine: a new radioligand for labelling α7-type neuronal nicotinic acetylcholine receptors.  Neuropharmacology. 1999;  38 679-90
  • 14 Cheng Y -C, Prusoff W H. Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.  Biochem Pharmacol. 1973;  22 3099-108

Prof. Dr. Gabriele M. König

Institute for Pharmaceutical Biology

University of Bonn

Nußallee 6

53115 Bonn

Germany

Phone: +49 228 733747

Fax: +49 228 733250

Email: g.koenig@uni-bonn.de

URL: http://www.uni-bonn.de/pharmbio/queen/GAWK.html

    >