57086-93-8

Usage

Uses

alpha-Linolenoyl Ethanolamide is an endocannabinoid containing a-linolenic acid.

Upstream product

• 59044-29-0 cis,cis,cis-9,12,15-octadecatrienoyl chloride 
• 141-43-5 ethanolamine 
• 1191-41-9 ethyl linolenate 
• 6114-24-5 ethyl linolenate 
• 463-40-1 (9Z,12Z,15Z)-octadeca-9-12,15-trienoic acid 

Relevant academic research and scientific papers

Synthesis of fatty-acid ethanolamides from Linum catharticum oils and Cololabis saira fats

Ethanolamides of polyunsaturated fatty acids (9Z,12Z,15Z-octadecatrienoic; 5Z,8Z,11Z,14Z,17Z-eicosapentaenoic; and 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic) and mixtures of ethanolamides of fatty acids from natural fats (oils) were synthesized. It was found that the polyunsaturated fatty acids did not isomerize under the proposed conditions for aminolysis of the ester bond. Conditions for analyzing the complicated mixtures of ethanolamides of fatty acids by HPLC-MS were determined.

Structure-Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo

A series of unsaturated fatty acids in fish oil and their corresponding ethanolamide metabolites were explored to find active fish oil components of antiallergic activity in vitro. Ethanolamides of omega-3 fatty acids (α-linolenic acid, EPA, and DHA) were found to possess promising antiallergic activity, whereas free fatty acids and ethanolamides of other fatty acids exhibited no or weak potency. Based on this finding, structure-activity relationships of DHA-ethanolamide (DHEA) derivatives were investigated to yield better fatty acid derivatives with enhanced antiallergic activity in vitro and in vivo. When the ethanolamide moiety of DHEA was replaced by the substituted sulfonamide functionality, highly promising potency was provided in vitro. Compound 59 showed improved antiallergic activity in vivo over DHEA. The results indicate that optimized DHEA derivatives have enhanced antiallergic activity in vitro and in vivo, and the resulting structures will be an important basis for further development of bioavailable derivatives with promising allergy suppressive activity.

Improved enzymatic procedure for the synthesis of anandamide and N-fatty acylalkanolamine analogues: A combination strategy to antitumor activity

Twenty N-fatty acylamines from linolenic and arachidonic acids, fifteen of them new compounds, were obtained through Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields and with high chemoselectivity. The optimal reaction conditions were achieved by studying the reaction parameters (temperature, E/S ratio, alcohol and alkanolamine/fatty acid ratio, time, solvent, free-solvent system, etc.). To identify ideal enzymatic methods for generating the alkanolamides we evaluated enzyme performance in three procedures: i) aminolysis of ethyl ester, ii) direct condensation between the fatty acid and the alkanolamine, and iii) a one-pot/two-step conversion of fatty acids into alkanolamides via in situ formation of the ethyl ester and subsequent aminolysis by the alkanolamine. The advantages noted with the enzymatic methodology, such as mild reaction conditions and low environmental impact, underscore biocatalysis as a convenient way to prepare the reported compounds. The cytotoxic activities of all compounds and mixtures of anandamide and its analogues were evaluated in rat glioma C6 cells. These studies reveal that some anandamide analogues enhance the antitumor effects of anandamide, suggesting their possible application as therapeutic tools in cancer treatment. Twenty N-fatty acylamines from linolenic and arachidonic acids were obtained by one-pot/two-step Candida antarctica B lipase-catalyzed esterification and aminolysis reactions in very good yields with high chemoselectivity. Cytotoxicity assays using rat glioma C6 cells revealed that some analogues enhanced the antitumor effects of anandamide (AEA), suggesting possible anticancer applications.

Optimized synthesis and characterization of N-acylethanolamines and O-acylethanolamines, important family of lipid-signalling molecules

The endocannabinoid anandamide (N-arachidonoylethanolamine, AEA), a physiologically occurring bioactive compound on CB1 and CB2 receptors, has multiple physiological functions. Since the discovery of AEA additional non-cannabinoid endogenous compounds such as N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA) have been identified from mammalian tissues. Virodhamine (O-arachidonoylethanolamine, VA) is the only identified new member of the endocannabinoid family that is characterised by an ester linkage between acylic acid and ethanolamine instead of the amide linkage found in AEA and others non-cannabinoid N-acylethanolamines. It has been reported, as a cautionary note for lipid analyses, that VA can be produced nonenzymatically from AEA (and vice versa) as consequence of O,N-acyl migrations. O,N-acyl migrations are well documented in synthetic organic chemistry literature, but are not well described or recognized with regard to methods in lipid isolation or lipid enzyme studies. We here report an economical and effective protocol for large scale synthesis and characterization of some N- and O-acylethanolamines that could be useful as reference standards in order to investigate their possible formation in biological membranes, with potentially interesting biological properties.

Evaluation of endogenous fatty acid amides and their synthetic analogues as potential anti-inflammatory leads

A series of endogenous fatty acid amides and their analogues (1-78) were prepared, and their inhibitory effects on pro-inflammatory mediators (NO, IL-1β, IL-6, and TNF-α) in LPS-activated RAW264.7 cells were evaluated. Their inhibitory activity on the pro-inflammatory chemokine MDC in IFN-γ-activated HaCaT cells was also examined. The results showed that the activity is strongly dependent on the nature of the fatty acid part of the molecules. As expected, the amides derived from enone fatty acids showed significant activity and were more active than those derived from other types of fatty acids. A variation of the amine headgroup also altered bioactivity profile remarkably, possibly by modulating cell permeability. Regarding the amine part of the molecules, N-acyl dopamines exhibited the most potent activity (IC50 ～2 μM). This is the first report of the inhibitory activity of endogenous fatty acid amides and their analogues on the production of nitric oxide, cytokines (IL-1β, IL-6, and TNF-α) and the chemokine MDC. This study suggests that the enone fatty acid-derived amides (such as N-acyl ethanolamines and N-acyl amino acids) and N-acyl dopamines may be potential anti-inflammatory leads.

Selective synthesis of unsaturated N-acylethanolamines by lipase-catalyzed N-acylation of ethanolamine with unsaturated fatty acids

The selective synthesis of unsaturated N-acylethanolamines 1b-6b by lipase-catalyzed direct condensation between unsaturated fatty acids 1a-6a and ethanolamine is reported. Reactions were carried out in hexane at 40 °C, in the presence of Candida antarctica Lipase B as the catalyst, to give the corresponding amides 1b-6b with yields ranging from 80 to 88%.

Anandamide inhibits nuclear factor-κB activation through a cannabinoid receptor-independent pathway

Anandamide (arachidonoylethanolamine, AEA), an endogenous agonist for both the cannabinoid CB, receptor and the vanilloid VR1 receptor, elicits neurobehavioral, anti-inflammatory, immunomodulatory, and proapoptotic effects. Because of the central role of nuclear factor-κB (NF-κB) in the inflammatory process and the immune response, we postulated that AEA might owe some of its effects to the suppression of NF-κB. This study shows that AEA inhibits tumor necrosis factor-α (TNFα)-induced NF-κB activation by direct inhibition of the IκB kinase (IKK)β and, to a lesser extent, the IKKα subunits of κB inhibitor (IκB) kinase complex, and that IKKs inhibition by AEA correlates with inhibition of IκBα degradation, NF-κB binding to DNA, and NF-κB-dependent transcription in TNFα-stimulated cells. AEA also prevents NF-κB-dependent reporter gene expression induced by mitogen-activated protein kinase kinase kinase and NF-κB-inducing kinase. The NF-κB inhibitory activity of AEA was independent of CB1 and CB2 activation in TNFα-stimulated 5.1 and A549 cell lines, which do not express vanilloid receptor 1, and was not mediated by hydrolytic products formed through the activity of the enzyme fatty acid amide hydrolase. Chemical modification markedly affected AEA inhibitory activity on NF-κB, suggesting rather narrow structure-activity relationships and the specific interaction with a molecular target. Substitution of the alkyl moiety with less saturated fatty acids generally reduced or abolished activity. However, replacement of the ethanolamine "head" with a vanillyl group led to potent inhibition of TNFα-induced NF-κB-dependent transcription. These findings provide new mechanistic insights into the anti-inflammatory and proapoptotic activities of AEA, and should foster the synthesis of improved analogs amenable to pharmaceutical development as anti-inflammatory agents.