Subscribe to RSS
DOI: 10.1055/s-2004-832610
© Georg Thieme Verlag KG Stuttgart · New York
Prenylated Indole Alkaloids from Flustra foliacea with Subtype Specific Binding on NAChRs
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.
Key words
Flustra foliacea - alkaloids - nicotinic acetylcholine receptors
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