236743-58-1Relevant academic research and scientific papers
Pig Liver Esterases Hydrolyze Endocannabinoids and Promote Inflammatory Response
Zhou, Qiongqiong,Yan, Bingfang,Sun, Wanying,Chen, Qi,Xiao, Qiling,Xiao, Yuncai,Wang, Xiliang,Shi, Deshi
, (2021/06/07)
Endocannabinoids are endogenous ligands of cannabinoid receptors and activation of these receptors has strong physiological and pathological significance. Structurally, endocannabinoids are esters (e.g., 2-arachidonoylglycerol, 2-AG) or amides (e.g., N-arachidonoylethanolamine, AEA). Hydrolysis of these compounds yields arachidonic acid (AA), a major precursor of proinflammatory mediators such as prostaglandin E2. Carboxylesterases are known to hydrolyze esters and amides with high efficiency. CES1, a human carboxylesterase, has been shown to hydrolyze 2-AG, and shares a high sequence identity with pig carboxylesterases: PLE1 and PLE6 (pig liver esterase). The present study was designed to test the hypothesis that PLE1 and PLE6 hydrolyze endocannabinoids and promote inflammatory response. Consistent with the hypothesis, purified PLE1 and PLE6 efficaciously hydrolyzed 2-AG and AEA. PLE6 was 40-fold and 3-fold as active as PLE1 towards 2-AG and AEA, respectively. In addition, both PLE1 and PLE6 were highly sensitive to bis(4-nitrophenyl) phosphate (BNPP), an aryl phosphodiester known to predominately inhibit carboxylesterases. Based on the study with BNPP, PLEs contributed to the hydrolysis of 2-AG by 53.4 to 88.4% among various organs and cells. Critically, exogenous addition or transfection of PLE6 increased the expression and secretion of proinflammatory cytokines in response to the immunostimulant lipopolysaccharide (LPS). This increase was recapitulated in cocultured alveolar macrophages and PLE6 transfected cells in transwells. Finally, BNPP reduced inflammation trigged by LPS accompanied by reduced formation of AA and proinflammatory mediators. These findings define an innovative connection: PLE-endocannabinoid-inflammation. This mechanistic connection signifies critical roles of carboxylesterases in pathophysiological processes related to the metabolism of endocannabinoids.
Synthesis of 14,15-EET from Arachidonic Acid Using Urea-Hydrogen Peroxide as the Oxidant
Xie, Fuchun,Li, Bingbing X.,Alkayed, Nabil J.,Xiao, Xiangshu
, p. 105 - 110 (2015/10/20)
14,15- Epoxyeicosatrienoic acid (14,15-EET) is an endogenous bioactive lipid with pharmacological benefits in multiple cardiovascular diseases. We describe here a practical synthesis of 14,15-EET from arachidonic acid using urea-hydrogen peroxide (UHP) as the oxidant.
Endocannabinoids anandamide and 2-arachidonoylglycerol are substrates for human CYP2J2 epoxygenase
McDougle, Daniel R.,Kambalyal, Amogh,Meling, Daryl D.,Das, Aditi
, p. 616 - 627 (2015/01/16)
The endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are arachidonic acid (AA) derivatives that are known to regulate human cardiovascular functions. CYP2J2 is the primary cytochrome P450 in the human heart and is most well known for the metabolism of AA to the biologically active epoxyeicosatrienoic acids. In this study, we demonstrate that both 2-AG and AEA are substrates for metabolism by CYP2J2 epoxygenase in the model membrane bilayers of nanodiscs. Reactions of CYP2J2 with AEA formed four AEA-epoxyeicosatrienoic acids, whereas incubations with 2-AG yielded detectable levels of only two 2-AG epoxides. Notably, 2-AG was shown to undergo enzymatic oxidative cleavage to form AA through a NADPH-dependent reaction with CYP2J2 and cytochrome P450 reductase. The formation of the predominant AEA and 2-AG epoxides was confirmed using microsomes prepared from the left myocardium of porcine and bovine heart tissues. The nuances of the ligand-protein interactions were further characterized using spectral titrations, stopped-flow small-molecule ligand egress, and molecular modeling. The experimental and theoretical data were in agreement, which showed that substitution of the AA carboxylic acid with the 2-AG ester-glycerol changes the binding interaction of these lipids within the CYP2J2 active site, leading to different product distributions. In summary, we present data for the functional metabolomics of AEA and 2-AG by a membrane-bound cardiovascular epoxygenase.
Synthesis of all-trans arachidonic acid and its effect on rabbit platelet aggregation
Anagnostopoulos, Dimitris,Chatgilialoglu, Chryssostomos,Ferreri, Carla,Samadi, Abdelouahid,Siafaka-Kapadai, Athanassia
, p. 2766 - 2770 (2007/10/03)
A simple and high-yielding method to convert natural all-cis PUFA derivatives to the corresponding all-trans geometrical isomers is described. The method is based on the thiyl radical-catalyzed cis-trans isomerization. The all-trans isomer of arachidonic acid was found to cause rabbit platelet aggregation at concentrations higher than 0.1 mM and inhibition of PAF-induced platelet aggregation in a concentration dependent manner with an IC50 in the micromolar range.
Solid-phase synthesis of anandamide analogues
Qi, Longwu,Meijler, Michael M.,Lee, Sang-Hyeup,Sun, Chengzao,Janda, Kim D.
, p. 1673 - 1675 (2007/10/03)
The endocannabinoids are amides and esters of arachidonic acid that can mimic the pharmacological properties of Δ9-tetrahydrocannabinol (Δ9-THC). Anandamide, the most prominent of the endocannabinoids, has been implicated in both metabolic/physiological roles of the central nervous system, making it an attractive medicinal target. As such, we report the first solid-phase methodology that expedites access to various anandamide analogues. Our synthesis features a repetitive Cu-mediated coupling reaction between terminal alkynes and propargyl halides or allylic halides.
Synthesis of Arachidonic Acid and Its Acetylenic Precursor
Ivanov, I. V.,Groza, N. V.,Mnasina, E. E.,Myagkova, G. I.
, p. 696 - 699 (2007/10/03)
(5Z,8Z,11Z,14Z)-Eicosatetraenoic (arachidonic) acid and its precursor, 5,8,11,14-eicosatetraynoic acid, were synthesized by the polyacetylene approach using the cross coupling of propargyl iodides and highly reactive organometallic complexes of terminal acetylenic synthons formed in situ. - Key words: arachidonic acid; 5,8,11,14-eicosatetraynoic acid; cross coupling; copper(I) catalysis
Cleavage of Esters under Nearly Neutral Conditions at High Pressure. Chemo- and Regioselective Hydrolysis in Organic Solvents
Yamamoto, Yoshinori,Furuta, Toshiaki,Matsuo, Jiro,Kurata, Tetsuro
, p. 5737 - 5738 (2007/10/02)
Hydrolysis of esters proceeded at room temperature under high pressure in the presence of iPr2NEt or N-methylmorpholine using CH3CN-H2O (60:1) as the solvent.This very mild procedure enables the smooth hydrolysis of biologically important compounds such as amino esters, aliphatic unsaturated fatty esters, and β-hydroxy esters; no racemization, no isomerization, and no side reactions take place.
Terpenoids and Phenolics from Cassia tora Stem Bark
Chakrabarty, Kakoli,Chawla, Mahindra H.
, p. 1165 - 1166 (2007/10/02)
The first natural occurance of 3,5,8,3',4',5'-hexahydroxyflavone and a hydroxycoumarin, aurapterol from Cassia tora stem bark is reported.Euphol, basseol, emodin, rhein, palmitic acid, isostearic acid, behenic acid, ethyl arachidate and β-sitosterol have also been isolated from this source the first time.
