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Self-assembling cannabinomimetics: supramolecular structures of N-alkyl amides.
MedLine Citation:
PMID:  17497806     Owner:  NLM     Status:  MEDLINE    
Certain fatty acid N-alkyl amides from the medicinal plant Echinacea activate cannabinoid type-2 (CB2) receptors. In this study we show that the CB2-binding Echinacea constituents dodeca-2E,4E-dienoic acid isobutylamide (1) and dodeca-2E,4E,8Z,10Z-tetraenoic acid isobutylamide (2) form micelles in aqueous medium. In contrast, micelle formation is not observed for undeca-2E-ene-8,10-diynoic acid isobutylamide (3), which does not bind to CB2, or structurally related endogenous cannabinoids, such as arachidonoyl ethanolamine (anandamide). The critical micelle concentration (CMC) range of 1 and 2 was determined by fluorescence spectroscopy as 200-300 and 7400-10000 nM, respectively. The size of premicelle aggregates, micelles, and supermicelles was studied by dynamic light scattering. Microscopy images show that compound 1, but not 2, forms globular and rod-like supermicelles with radii of approximately 75 nm. The self-assembling N-alkyl amides partition between themselves and the CB2 receptor, and aggregation of N-alkyl amides thus determines their in vitro pharmacological effects. Molecular mechanics by Monte Carlo simulations of the aggregation process support the experimental data, suggesting that both 1 and 2 can readily aggregate into premicelles, but only 1 spontaneously assembles into larger aggregates. These findings have important implications for biological studies with this class of compounds.
Stefan Raduner; William Bisson; Ruben Abagyan; Karl-Heinz Altmann; Jürg Gertsch
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Publication Detail:
Type:  Journal Article     Date:  2007-05-11
Journal Detail:
Title:  Journal of natural products     Volume:  70     ISSN:  0163-3864     ISO Abbreviation:  J. Nat. Prod.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-22     Completed Date:  2007-08-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906882     Medline TA:  J Nat Prod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1010-5     Citation Subset:  IM    
Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.
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MeSH Terms
Amides / chemistry*,  isolation & purification,  pharmacokinetics
Arachidonic Acids / chemistry,  pharmacokinetics
Cyclohexanols / pharmacology
Echinacea / chemistry*
Models, Biological
Molecular Structure
Plants, Medicinal / chemistry*
Polyunsaturated Alkamides / chemistry,  pharmacokinetics
Receptor, Cannabinoid, CB2 / drug effects*
Reg. No./Substance:
0/Amides; 0/Arachidonic Acids; 0/Cyclohexanols; 0/Polyunsaturated Alkamides; 0/Receptor, Cannabinoid, CB2; 83003-12-7/3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; 94421-68-8/anandamide

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