[Epub ahead of print]
N-Alkyl dien- and trienamides from the roots of Otanthus maritimus with binding affinity for opioid and cannabinoidreceptors.
Source
Institute of Translational Pharmacology, UOS of Cagliari, National Research Council, Parco Scientifico e Tecnologico-Pula, Cagliari, Italy.
Abstract
Two new thienylheptatrienamides (1, 5) and one new neo-lignan (12), together with thirteen known compounds (2, 3, 4, 6-11, 13-16) were isolated from the roots of Otanthus maritimus. The structures of the new compounds were elucidated on the basis of extensive 1D and 2D NMR experiments as well as high resolution mass spectrometry. All the isolated amides (1-10), the known pontica epoxide (11) and the new neo-lignan (12) were evaluated for their binding affinity to the CB1 and CB2 as well as to the μ and δ opioid receptors. Some alkylamides showed moderately high binding affinity for CB2 receptors and 1-[(2E,4E,8Z)-tetradecatrienoyl]piperidine (10) resulted the most active one with a Ki value of 160nM. As far as we know, this is the first example of a tertiary alkylamide that binds CB2 receptors with significant potency. Compounds that showed the highest affinity forcannabinoid receptors (6-8, 10) were much less potent against opioid receptors. Primary structure-activity relationship is discussed. Docking experiments were carried out with the aim to understand the key interactions of the most active compounds with CB2 receptor.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Copyright © 2013 Elsevier Ltd. All rights reserved.
KEYWORDS:
Alkylamides, Cannabinoid receptors, Molecular modeling, NMR, Opioid receptors, Otanthus maritimus
- PMID:
- 24095014
- [PubMed – as supplied by publisher]
