Identification of endocannabinoid system-modulating N-alkylamides from Heliopsis helianthoides var. scabra and Lepidium meyenii.


Autoria(s): Hajdu, Zsanett; Nicolussi, Simon; Rau, Mark; Lorántfy, László; Forgo, Peter; Hohmann, Judit; Csupor, Dezső; Gertsch, Jürg
Data(s)

25/07/2014

Resumo

The discovery of the interaction of plant-derived N-alkylamides (NAAs) and the mammalian endocannabinoid system (ECS) and the existence of a plant endogenous N-acylethanolamine signaling system have led to the re-evaluation of this group of compounds. Herein, the isolation of seven NAAs and the assessment of their effects on major protein targets in the ECS network are reported. Four NAAs, octadeca-2E,4E,8E,10Z,14Z-pentaene-12-ynoic acid isobutylamide (1), octadeca-2E,4E,8E,10Z,14Z-pentaene-12-ynoic acid 2'-methylbutylamide (2), hexadeca-2E,4E,9Z-triene-12,14-diynoic acid isobutylamide (3), and hexadeca-2E,4E,9,12-tetraenoic acid 2'-methylbutylamide (4), were identified from Heliopsis helianthoides var. scabra. Compounds 2-4 are new natural products, while 1 was isolated for the first time from this species. The previously described macamides, N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (5), N-benzyl-(9Z,12Z,15Z)-octadecatrienamide (6), and N-benzyl-(9Z,12Z)-octadecadienamide (7), were isolated from Lepidium meyenii (Maca). N-Methylbutylamide 4 and N-benzylamide 7 showed submicromolar and selective binding affinities for the cannabinoid CB1 receptor (Ki values of 0.31 and 0.48 μM, respectively). Notably, compound 7 also exhibited weak fatty acid amide hydrolase (FAAH) inhibition (IC50 = 4 μM) and a potent inhibition of anandamide cellular uptake (IC50 = 0.67 μM) that was stronger than the inhibition obtained with the controls OMDM-2 and UCM707. The pronounced ECS polypharmacology of compound 7 highlights the potential involvement of the arachidonoyl-mimicking 9Z,12Z double-bond system in the linoleoyl group for the overall cannabimimetic action of NAAs. This study provides additional strong evidence of the endocannabinoid substrate mimicking of plant-derived NAAs and uncovers a direct and indirect cannabimimetic action of the Peruvian Maca root.

Formato

application/pdf

Identificador

http://boris.unibe.ch/66268/1/Hajdu%20Nicolussi%20Rau.pdf

Hajdu, Zsanett; Nicolussi, Simon; Rau, Mark; Lorántfy, László; Forgo, Peter; Hohmann, Judit; Csupor, Dezső; Gertsch, Jürg (2014). Identification of endocannabinoid system-modulating N-alkylamides from Heliopsis helianthoides var. scabra and Lepidium meyenii. Journal of natural products, 77(7), pp. 1663-1669. American Chemical Society 10.1021/np500292g <http://dx.doi.org/10.1021/np500292g>

doi:10.7892/boris.66268

info:doi:10.1021/np500292g

info:pmid:24972328

urn:issn:0163-3864

Idioma(s)

eng

Publicador

American Chemical Society

Relação

http://boris.unibe.ch/66268/

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Hajdu, Zsanett; Nicolussi, Simon; Rau, Mark; Lorántfy, László; Forgo, Peter; Hohmann, Judit; Csupor, Dezső; Gertsch, Jürg (2014). Identification of endocannabinoid system-modulating N-alkylamides from Heliopsis helianthoides var. scabra and Lepidium meyenii. Journal of natural products, 77(7), pp. 1663-1669. American Chemical Society 10.1021/np500292g <http://dx.doi.org/10.1021/np500292g>

Palavras-Chave #570 Life sciences; biology #610 Medicine & health
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed