- Synthesis and biological evaluation of novel tacrine derivatives and tacrine-coumarin hybrids as cholinesterase inhibitors
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A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds,
- Hamulakova, Slavka,Janovec, Ladislav,Hrabinova, Martina,Spilovska, Katarina,Korabecny, Jan,Kristian, Pavol,Kuca, Kamil,Imrich, Jan
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Read Online
- Modified coumarins. 14. Synthesis of 7-hydroxy-[4,3′]dichromenyl-2, 2′-dione derivatives
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New derivatives of 3-(2-oxochromen-4-yl)chromen-2-one, modified analogs of natural dicoumarins, were prepared from substituted coumarin-4-acetic acids.
- Dubovik,Garazd,Khilya
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Read Online
- Design and synthesis of novel coumarin derivatives as potential acetylcholinesterase inhibitors for Alzheimer's disease
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Twenty novel 7-benzyloxycoumarin based compounds were synthesized with a variety of bioactive chemical fragments. The synthesized compounds showed remarkable acetylcholinesterase (AChE) inhibitory activity. In vitro assay revealed that compounds 7-benzyloxy-4-{[(4-phenylthiazol-2(3H)-ylidene)hydrazono]methyl}-2H-chromen-2-one (5b, IC50= 0.451μM), 7-benzyloxy-4-({[4-(4-methoxyphenyl)thiazol-2(3H)-ylidene]hydrazono}methyl)-2H-chromen-2-one (5d, IC50= 0.625μM), 5-amino-1-[2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-1H-pyrazole-4-carbonitrile (13c, IC50= 0.466μM), 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)-N-(2-methylimino-4-phenylthiazol-3(2H)-yl)acetamide (16a, IC50= 0.500μM) and 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)-N-[4-(4-methoxyphenyl)-2-methyliminothiazol-3(2H)-yl]acetamide (16b, IC50= 0.590μM) exhibited promising AChE inhibitory activity even better than donepezil (IC50= 0.711μM). Kinetic study for compound 5b implied mixed type inhibitor which could bind peripheral anionic site (PAS) and catalytic active site (CAS) of AChE enzyme. In addition, in vivo evaluation of compounds 5b, 13c and 16a confirmed significant memory improvement in scopolamine-induced impairment model in tested mice. Furthermore, in silico studies were performed on the synthesized compounds which included molecular docking study at the active site of recombinant human acetylcholinesterase enzyme (rhAChE) as well as prediction of ADMET and other physicochemical parameters. A correlation between the docking results and IC50 of tested compounds was routinely observed and shared similar binding pattern to the co-crystallized ligand donepezil.
- Amin, Kamilia M.,Abdel Rahman, Doaa E.,Abdelrasheed Allam, Heba,El-Zoheiry, Haidy H.
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- Readily functionalizable phosphonium-tagged fluorescent coumarins for enhanced detection of conjugates by mass spectrometry
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Fluorescent coumarins are an important class of small-molecule organic fluorophores ubiquitous in different well-established and emerging fields of research including, among others, biochemistry and chemical biology. The present work aims at covering the poor detectability of coumarin-based conjugates by mass spectrometry while keeping important photophysical properties of the coumarin core. In this context, the synthesis of readily functionalizable phosphonium-tagged coumarin derivatives enabling a dual mass-tag and fluorescence labelling of analytes or (bio)molecules of interest through a single-step protocol, is reported. The utility of these coumarins is illustrated through the preparation of fluorogenic substrates that facilitated identification of the peptide fragment released by specific proteolytic cleavages.
- Lizzul-Jurse, Antoine,Bailly, Laetitia,Hubert-Roux, Marie,Afonso, Carlos,Renard, Pierre-Yves,Sabot, Cyrille
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supporting information
p. 7777 - 7791
(2016/08/24)
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- Preparation and pharmacological effects of coumarin derivative and application of coumarin derivative to treatment on pruritus
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The invention relates to preparation of a coumarin derivative 7,8-dihydroxy-4-trifluoromethyl-chromene-2H-chromen-2-one for treating the pruritus symptom, studies of pharmacodynamics on the aspects of a molecular pharmacology mechanism, a pruritus animal model and the like of the coumarin derivative, and a pharmaceutics study applicable to treatment on pruritus. The active compound is definite in pharmacological effect mechanism, is broad-spectrum and effective to treat the pruritus symptom, and can be used for clinical application to treatment on skin diseases.
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Paragraph 0082; 0083; 0084
(2016/11/17)
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- Development of fluorescent peptide substrates and assays for the key autophagy-initiating cysteine protease enzyme, ATG4B
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Abstract An efficient assay for monitoring the activity of the key autophagy-initiating enzyme ATG4B based on a small peptide substrate has been developed. A number of putative small fluorogenic peptide substrates were prepared and evaluated and optimized
- Vezenkov, Lubomir,Honson, Nicolette S.,Kumar, Nag S.,Bosc, Damien,Kovacic, Suzana,Nguyen, Thanh G.,Pfeifer, Tom A.,Young, Robert N.
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supporting information
p. 3237 - 3247
(2015/08/03)
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- A versatile access to new halogenated 7-azidocoumarins for photoaffinity labeling: Synthesis and photophysical properties
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A versatile methodology for the synthesis of 6/8-halogenated 7-aminocoumarins from the corresponding 7-hydroxy analogs using Pd-catalyzed amination reaction as the key step is presented. Further readily conversion into 7-azidocoumarins was performed and the resulting aryl azides proved higher stability and reactivity than the corresponding non-halogenated parent compound. These new compounds may thus constitute attractive scaffolds for designing novel photoaffinity reagents for various challenging bio-labeling applications.
- Punescu, Emilia,Louise, Ludivine,Jean, Ludovic,Romieu, Anthony,Renard, Pierre-Yves
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experimental part
p. 427 - 434
(2012/06/29)
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- Fluorescent probe for detection of fluoride in water and bioimaging in A549 human lung carcinoma cells
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We have successfully developed a fluoride ion probe for fluorescence cell bioimaging - desirable properties include retention of the fluorophore inside cells, non-cytotoxicity to mammalian cells, appreciable solubility in water, and stoichiometric reactio
- Kim, Soon Young,Park, Jongmin,Koh, Minseob,Park, Seung Bum,Hong, Jong-In
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supporting information; scheme or table
p. 4735 - 4737
(2010/01/16)
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- Designing better coumarin-based fluorogenic substrates for PTP1B
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As part of a program to develop better PTP1B fluorogenic substrates that more closely mimic the functionality found in the natural substrate, we have prepared and evaluated nine novel analogs of 4-methylumbelliferone phosphate (MUP) with a variety of additional groups occupying the second phosphate binding pocket.
- Holmes, Christopher P.,Macher, Natalie,Grove, J. Russell,Jang, Larry,Irvine, Jennifer D.
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body text
p. 3382 - 3385
(2009/04/11)
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- Synthesis, anti-tubercular activity and 3D-QSAR study of coumarin-4-acetic acid benzylidene hydrazides
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A set of 25 coumarin-4-acetic acid benzylidene hydrazides were synthesized and characterized by NMR, IR and mass spectroscopic techniques. The compounds were evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 system to determine percentage inhibition. To understand the relationship between structure and activity, a 3D-QSAR analysis has been carried out by Comparative Molecular Field Analysis (CoMFA). Several statistically significant CoMFA models were generated. The CoMFA model generated with database alignment was the best in terms of overall statistics. The CoMFA contours provide a good insight into the structure activity relationships of the compounds reported herein.
- Manvar, Atul,Malde, Alpeshkumar,Verma, Jitender,Virsodia, Vijay,Mishra, Arun,Upadhyay, Kuldip,Acharya, Hrishikesh,Coutinho, Evans,Shah, Anamik
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p. 2395 - 2403
(2008/12/23)
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- Profiling of glycosidase activities using coumarin-conjugated glycoside cocktails
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Glycosidases are a large subgroup of carbohydrate-processing enzymes that hydrolytically cleave the glycosidic bond. Glycans formed by the action of glycosidases are involved in various biological processes. Genetic abnormalities in glycosidases are associated with inherited diseases. Thus, characterization of the catalytic activities of glycosidases is of great importance. Herein, we describe a simple and rapid approach for determining glycosidase activity profiles using coumarin-conjugated glycoside cocktails.
- Park, Sungjin,Shin, Injae
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p. 619 - 622
(2007/10/03)
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- 4,4′-spirodichroman-2-ones as unexpected products from the condensation of resorcinols and dimethyl acetonedicarboxylate
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As a result of the reaction of resorcinols with dimethyl acetonedicarboxylate under the conditions of the Pechmann reaction derivatives of 4,4′-spirodichroman-2-one were isolated as anomalous condensation products. Their structure was demonstrated by spectral methods. A mechanism was proposed for the formation of the spirodilactone system.
- Dubovik,Garazd,Khilya
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p. 277 - 281
(2008/09/20)
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- ZrCl4-catalyzed Pechmann reaction: Synthesis of coumarins under solvent-free conditions
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Zirconium (IV) chloride is used as an efficient catalyst in the Pechmann condensation reaction of phenols with β-keto esters leading to the formation of coumarin derivatives in good yields under solvent-free conditions.
- Smitha,Reddy, Ch. Sanjeeva
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p. 3997 - 4003
(2007/10/03)
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- Enzymatic profiling system in a small-molecule microarray.
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[reaction: see text] We have developed a microarray-based strategy for detection of three major classes of hydrolytic enzymes on the basis of their catalytic activities. This enables the sensitive detection of proteins not merely by their bindings but rat
- Zhu, Qing,Uttamchandani, Mahesh,Li, Dongbo,Lesaicherre, Marie L,Yao, Shao Q
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p. 1257 - 1260
(2007/10/03)
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