40140-09-8Relevant academic research and scientific papers
An Activity-Based Sensing Approach for the Detection of Cyclooxygenase-2 in Live Cells
Arango, Andres S.,Chan, Jefferson,Das, Aditi,Dong, Liang,Huff, Hannah C.,Malkowski, Michael G.,Reinhardt, Christopher J.,Tajkhorshid, Emad,Yadav, Anuj K.
, p. 3307 - 3314 (2020)
Cyclooxygenase-2 (COX-2) overexpression is prominent in inflammatory diseases, neurodegenerative disorders, and cancer. Directly monitoring COX-2 activity within its native environment poses an exciting approach to account for and illuminate the effect of the local environments on protein activity. Herein, we report the development of CoxFluor, the first activity-based sensing approach for monitoring COX-2 within live cells with confocal microscopy and flow cytometry. CoxFluor strategically links a natural substrate with a dye precursor to engage both the cyclooxygenase and peroxidase activities of COX-2. This catalyzes the release of resorufin and the natural product, as supported by molecular dynamics and ensemble docking. CoxFluor enabled the detection of oxygen-dependent changes in COX-2 activity that are independent of protein expression within live macrophage cells.
Effect of cosolvent on the lateral order of spontaneously formed amphiphilic amide two-dimensional crystallites at the air-solution interface
Weinbach, Susan P.,Jacquemain, Didier,Leveiller, Franck,Kjaer, Kristian,Als-Nielsen, Jens,Leiserowitz, Leslie
, p. 11110 - 11118 (1993)
At low temperature (5-12 °C), uncompressed films of insoluble amphiphilic molecules C19H39X, where the head group X contains one (CONH2, 1) or two (CONHC2H4CONH2, 2) amide groups, spontaneously form two-dimensional (2D) crystalline clusters over aqueous subphases containing soluble amide or carboxylic acid molecules. These crystallites were detected and their structures were studied using grazing incidence X-ray diffraction (GID). In the presence of subphases containing carboxylic acid (RCO2H, R = H, CH2Cl) at sufficiently high concentrations, a loss of diffraction signal was observed for 1, while amide and less concentrated acid subphases did not show such a destructive effect. The effect of the subphase solute molecules was understood in terms of the different ways in which the solutes hydrogen bond to the amide head groups of the amphiphiles. Both amide and acid solute molecules can form hydrogen-bonded cyclic dimers with the amide head groups. With an amide subphase, such dimers lead to an extension of the hydrogen-bonding network of the crystallites, and thus enhance its stability, but acid molecules may also bind to the monolayer at low concentrations with less than full occupancy. At high acid concentration, and thus more extensive formation of cyclic dimers between carboxylic acid and amphiphilic amide molecules, repulsive interactions between lone pair electrons on oxygen atoms of bound acid molecules inhibit formation of ordered arrays of these dimers and lead to a lack of diffraction signal. In 2, the second amide group strengthens the crystallites to the extent that there is no decrease in crystallinity over a 1 M formic acid subphase. The shape of the intensity profiles of the Bragg rods and the specular X-ray reflectivity measurements of 2 indicate formation of molecular trilayers.
FLUORESCENT PROBE FOR CYCLOOXYGENASE-2
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Paragraph 0109, (2021/10/30)
Cyclooxygenase-2 (COX-2) over-expression is prominent in inflammatory diseases, neurodegenerative disorders, and cancer. Directly monitoring COX-2 activity within its native environment poses an exciting approach to account for and illuminate the effect of the local environments on protein activity. Herein, we report the development of CoxFluor, the first activity-based sensing approach for monitoring COX-2 within live cells with confocal microscopy and flow cytometry. CoxFluor strategically links a natural substrate with a dye precursor to engage both the cyclooxygenase and peroxidase activities of COX-2. This catalyzes the release of resorufin and the natural product, as supported by molecular dynamics and ensemble docking. CoxFluor enabled the detection of oxygen-dependent changes in COX-2 activity that are independent of protein expression within live macrophage cells.
Method for efficiently synthesizing Aramchol
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Paragraph 0076; 0092-0094, (2020/05/01)
The invention discloses a method for efficiently synthesizing Aramchol. The method comprises the following steps: firstly, generating an intermediate b-methyl cholate through esterification reaction of methanol and cholic acid molecules; reacting an alkylbenzene sulfonyl chloride with a specific structure with methyl cholate in the presence of an acid-binding agent, and selectively reacting with 3-hydroxyl of cholic acid molecules to synthesize a key intermediate c-3 alpha-O-alkylbenzene sulfonyl methyl cholate; and then protecting free hydroxyl in the intermediate c, and removing the free hydroxyl after the amidation reaction is finished, so that the problems of side reaction of acyl chloride and the free hydroxyl, serious emulsification phenomenon in the reaction process and difficulty in separation are effectively avoided.
Characterization of the molecular packing, thermotropic phase behaviour and critical micellar concentration of a homologous series of N-acyltaurines (n = 9–18). PXRD, DSC and fluorescence spectroscopic studies
Arul Prakash, Sukanya,Kamlekar, Ravi Kanth
, (2020/06/22)
N-acyltaurines (NATs) are amides of fatty acids that can be structurally related to endocannabinoids. They show interesting physiological and pharmacological properties. We have synthesized a homologous series of NATs with saturated acyl chains (n = 9–18) and investigated their supramolecular structure and thermotropic phase transitions by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The d-spacings obtained from PXRD increase linearly with chain length with an increment of ～0.847 ? per additional CH2 moiety suggesting that NATs adopt a tilted bilayer structure with similar packing in crystal lattice. Results obtained from DSC studies indicate that the endothermic transition temperature (Tt) of NATs showed a gradually increasing trend with increasing acyl chain length. The enthalpy (ΔHt) and entropy (ΔSt) of transition show odd-even alternations with odd-chain compounds having higher values than the even-chain compounds. The critical micellar concentration (CMC) of NATs was determined in water at room temperature by fluorescence spectroscopy by monitoring the spectral changes of 8-anilinonaphthalene-1-sulfonic acid (ANS). The CMCs of NATs were found to decrease with increase in acyl chain length. The present results provide a thermodynamic and structural basis for investigating the interaction of NATs with other membrane lipids and proteins, which in turn can shed light in understanding how they function in vivo (in biological membranes).
ABUSE-RESISTANT LONG-ACTING RELEASE OPIOID PRODRUGS
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Paragraph 93; 95, (2020/07/31)
There are provided, prodrugs of opioid such as levorphanol or morphine, having enhanced physical and chemical stability to resist tampering and to make long- acting release formulations, and pharmaceutically accepted salts and solvates thereof. There are also provided methods of using the disclosed compounds as abuse deterrent products.
New technology for efficiently synthesizing Aramchol by utilizing cholic acid and arachidic acid as raw materials
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Paragraph 0055; 0072-0075, (2019/04/04)
The invention discloses a new technology for efficiently synthesizing Aramchol by utilizing cholic acid and arachidic acid as raw materials. According to the new technology disclosed by the invention,a 3- hydroxyl group of cholic acid is activated by selecting para-butyl benzene sulfonyl chloride in larger steric hindrance and the like, 3alpha-O-para-butyl benzene sulfonyl methyl cholate, chiral3-C can be attacked by an azide group just through a direction against an alkylbenzene sulfonyloxy group of a leaving group during a nucleophilic substitution reaction process of the 3alpha-O-para-butyl benzene sulfonyl methyl cholate and sodium azide, inversion of 3-C configuration of a product-3-azido methyl cholate is ensured, and a firm foundation is laid for controlling the optical purity ofa final product-Aramchol.
Set-up and validation of a high throughput screening method for human monoacylglycerol lipase (MAGL) based on a new red fluorescent probe
Miceli, Matteo,Casati, Silvana,Ottria, Roberta,Di Leo, Simone,Eberini, Ivano,Palazzolo, Luca,Parravicini, Chiara,Ciuffreda, Pierangela
, (2019/06/20)
Monoacylglycerol lipase (MAGL) is a serine hydrolase that has a key regulatory role in controlling the levels of 2-arachidonoylglycerol (2-AG), the main signaling molecule in the endocannabinoid system. Identification of selective modulators of MAGL enables both to provide new tools for investigating pathophysiological roles of 2-AG, and to discover new lead compounds for drug design. The development of sensitive and reliable methods is crucial to evaluate this modulatory activity. In the current study, we report readily synthesized long-wavelength putative fluorogenic substrates with different acylic side chains to find a new probe for MAGL activity. 7-Hydroxyresorufinyl octanoate proved to be the best substrate thanks to the highest rate of hydrolysis and the best Km and Vmax values. In addition, in silico evaluation of substrates interaction with the active site of MAGL confirms octanoate resorufine derivative as the molecule of choice. The well-known MAGL inhibitors URB602 and methyl arachidonylfluorophosphonate (MAFP) were used for the assay validation. The assay was highly reproducible with an overall average Z0 value of 0.86. The fast, sensitive and accurate method described in this study is suitable for low-cost high-throughput screening (HTS) of MAGL modulators and is a powerful new tool for studying MAGL activity.
Mesogenic 3,6-bis(4-hydroxyphenyl)-1,2,4,5-tetrazine alkanoate esters
Fouad, Farid,Khabouchi, Faycal,Nielsen, Alek,Twieg, Robert
, p. 82 - 90 (2019/02/24)
A novel series of 3,6-bis(4-hdroxyphenyl)-1,2,4,5-tetrazine alkanoate esters were synthesized and their mesogenic properties were studied using differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). The impact of changing the tail-core linkage from alkyl or alkoxy to ester is profound. Compared to the alkyl or alkoxy linkages, the ester linkage reduced mesogenic properties. Short-tailed compounds are non mesogenic (4a-4e), while long-tailed compounds (4f-4r) exhibit nematic phases. Unlike the alkyl or alkoxy tail series, none of the 18 presented esters in this series exhibits a smectic phase.
Prodrugs of Heteraromatic Compounds
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Paragraph 0118, (2016/03/01)
The present invention relates to prodrugs of parent drug compounds containing heteroaromatic NH groups.
