Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors--implications for early myasthenia gravis treatment
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
21397501
DOI
10.1016/j.bmcl.2011.02.047
PII: S0960-894X(11)00231-9
Knihovny.cz E-zdroje
- MeSH
- acetylcholinesterasa chemie genetika metabolismus MeSH
- ambenoniumchlorid chemie farmakologie MeSH
- benzenaminium, 4,4'-(3-oxo-1,5-pentandiyl)bis(N,N-dimethyl-N-2-propenyl-), dibromid chemie farmakologie MeSH
- butyrylcholinesterasa chemie genetika metabolismus MeSH
- chinolinové sloučeniny chemie farmakologie terapeutické užití MeSH
- cholinesterasové inhibitory chemie farmakologie terapeutické užití MeSH
- edrofonium chemie farmakologie MeSH
- kinetika MeSH
- lidé MeSH
- myasthenia gravis farmakoterapie MeSH
- rekombinantní proteiny chemie genetika metabolismus MeSH
- simulace molekulární dynamiky MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- ambenoniumchlorid MeSH
- benzenaminium, 4,4'-(3-oxo-1,5-pentandiyl)bis(N,N-dimethyl-N-2-propenyl-), dibromid MeSH
- butyrylcholinesterasa MeSH
- chinolinové sloučeniny MeSH
- cholinesterasové inhibitory MeSH
- edrofonium MeSH
- rekombinantní proteiny MeSH
This paper describes the preparation and in vitro evaluation of 18 newly prepared bis-quinolinium inhibitors on human recombinant acetylcholinesterase (AChE) and human plasmatic butyrylcholinesterase (BChE). Their inhibitory (IC(50)) and was compared to the chosen standards ambenonium dichloride, edrophonium chloride, BW284c51 and ethopropazine hydrochloride. One novel compound was found to be a promising inhibitor of hAChE (in nM range) and was better than edrophonium chloride or BW284c51, but was worse than ambenonium chloride. This compound also showed selectivity towards hAChE and it was confirmed as a non-competitive inhibitor of hAChE by kinetic analysis. A molecular modelling study further confirmed its binding to the peripheral active site of hAChE via apparent π-π or π-cationic interactions.
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