Source:http://linkedlifedata.com/resource/pubmed/id/21570751
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2011-6-13
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| pubmed:abstractText |
The synthesis and biochemical evaluation of new hybrids of tacrine (THA) and 4-fluorobenzoic acid (4-FBA) possessing activity towards acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition are presented. The compounds of interest were obtained from the reaction of activated 4-FBA and diamino derivatives of 1,2,3,4-tetrahydroacridine. The compounds C6-2KW/HCl, C6-4KW/HCl and C6-3KW/HCl have four-fold higher antiacetylcholinesterase activity than THA. All of the acquired compounds present higher selectivity towards AChE than THA and lower selectivity towards BuChE. In addition, a rapid, selective and stability-indicating HPLC method was developed and validated for the determination of C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl. THA and 4-FBA were found to be the main impurities. Chromatographic separation was achieved isocratically on a Waters Symmetry C18 150 × 3.9 mm, 4 ?m column with a mobile phase of acetonitrile/buffer (17 mM sodium dodecyl sulphate and 8.3 mM sodium dihydrogen phosphate, 50:50 v/v) (overall pH 4). A 1.5 ml/min flow rate and a 247 nm wavelength were chosen for this method. C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl were subjected to acidic and basic hydrolysis, chemical oxidation, thermal exposition at 60 °C and intense UV light. The limits of detection (LOD) and quantification (LOQ) were less than 2 ?g/ml and 6 ?g/ml for C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl, 0.04 ?g/ml and 0.12 ?g/ml for THA, 0.42 ?g/ml and 1.41 ?g/ml for 4-FBA, respectively.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-fluorobenzoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholinesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Acridines,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Butyrylcholinesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1768-3254
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
46
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3250-7
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| pubmed:meshHeading |
pubmed-meshheading:21570751-Acetylcholinesterase,
pubmed-meshheading:21570751-Acridines,
pubmed-meshheading:21570751-Alzheimer Disease,
pubmed-meshheading:21570751-Benzoic Acids,
pubmed-meshheading:21570751-Butyrylcholinesterase,
pubmed-meshheading:21570751-Cholinesterase Inhibitors,
pubmed-meshheading:21570751-Chromatography, High Pressure Liquid,
pubmed-meshheading:21570751-Drug Stability,
pubmed-meshheading:21570751-Enzyme Activation,
pubmed-meshheading:21570751-Humans,
pubmed-meshheading:21570751-Hydrolysis,
pubmed-meshheading:21570751-Kinetics,
pubmed-meshheading:21570751-Limit of Detection,
pubmed-meshheading:21570751-Oxidation-Reduction,
pubmed-meshheading:21570751-Sensitivity and Specificity,
pubmed-meshheading:21570751-Spectroscopy, Fourier Transform Infrared,
pubmed-meshheading:21570751-Structure-Activity Relationship,
pubmed-meshheading:21570751-Tacrine
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| pubmed:year |
2011
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| pubmed:articleTitle |
Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors.
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| pubmed:affiliation |
Medical University, Department of Pharmaceutical Chemistry and Drug Analyses, ul. Muszy?skiego 1, 90-151 Lodz, Poland. pawel.szymanski@umed.lodz.pl
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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