53832-58-9Relevant articles and documents
Different roles for the acyl chain and the amine leaving group in the substrate selectivity of N-Acylethanolamine acid amidase
Ghidini, Andrea,Scalvini, Laura,Palese, Francesca,Lodola, Alessio,Mor, Marco,Piomelli, Daniele
, p. 1411 - 1423 (2021/07/17)
N-acylethanolamine acid amidase (NAAA) is an N-terminal nucleophile (Ntn) hydrolase that catalyses the intracellular deactivation of the endogenous analgesic and anti-inflammatory agent palmitoylethanolamide (PEA). NAAA inhibitors counteract this process and exert marked therapeutic effects in animal models of pain, inflammation and neurodegeneration. While it is known that NAAA preferentially hydrolyses saturated fatty acid ethanolamides (FAEs), a detailed profile of the relationship between catalytic efficiency and fatty acid-chain length is still lacking. In this report, we combined enzymatic and molecular modelling approaches to determine the effects of acyl chain and polar head modifications on substrate recognition and hydrolysis by NAAA. The results show that, in both saturated and monounsaturated FAEs, the catalytic efficiency is strictly dependent upon fatty acyl chain length, whereas there is a wider tolerance for modifications of the polar heads. This relationship reflects the relative stability of enzyme-substrate complexes in molecular dynamics simulations.
COMPOSITIONS AND METHODS FOR THE MODULATION OF SPECIFIC AMIDASES FOR N-ACYLETHANOLAMINES FOR USE IN THE THERAPY OF INFLAMMATORY DISEASES
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Paragraph 0042, (2015/03/04)
The present invention regards compositions and methods for the modulation of amidases capable of hydrolysing N-acylethanolamines useable in the therapy of inflammatory diseases. In particular, the present invention regards a compound of general formula (I): enantiomers, diastereoisomers, racemes and mixtures, polymorphs, salts, solvates thereof, wherein: (a) R is a linear alkyl radical having 13 to 19 carbon atoms or alkenyl radical having 13 to 19 carbon atoms carrying a double bond; (b) X is 0 or S; (c) Y is a 2 or 3 carbon atom alkylene residue, optionally substituted with one or two groups equal or different from each other and selected from among the group consisting of: —CH3, —CH2OH, —COOCH3, —COOH. Y may preferably be: —CH2—CH2—, —CH2—CH2—CH2—, CH(CH3)—CH2—, —CH2—CH(CH3)—, —CH2—C(CH3)2—, —CH2—CH(CH2OH)—, —CH2—C((CH2OH)2)—, —CH═CH—, —CH2—CH(COOCH3)—, —CH2—CH(COOH)—, for use as a medicine.
Synthesis and anticonvulsant activity of N-(2-hydroxyethyl)amide derivatives
Guan, Li-Ping,Zhao, Dong-Hai,Xiu, Jing-Hui,Sui, Xin,Piao, Hu-Ri,Quan, Zhe-Shan
experimental part, p. 34 - 40 (2009/06/18)
A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.
