About: Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease

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About: Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	New tacrine derivatives 5a-d, 6a-d with piperazino-ethyl spacer linked with corresponding secondary amines and tacrine homodimer 8 were synthesized and tested as cholinesterase inhibitors on human acetylcholinesterase (hAChE) and human plasmatic butyrylcholinesterase (hBChE). In most cases the majority of synthesized derivatives exhibit a high AChE and BChE inhibitory activity with IC50 values in the low-nanomolar range, being clearly more potent than the reference standard tacrine (9-amino-1,2,3,4-tetrahydroacridine, 1) and 7-MEOTA (7-methoxy-9-amino-1,2,3,4-tetrahydroacridine). Among them, inhibitors 8 and 5c, showed a strong inhibitory activity against hAChE, with an IC50 value of 4.49 nM and 4.97, nM resp., and a high selectivity to hAChE. The compound 5d acted as the most potent inhibitor against hBChE with an IC50 value of 33.7 nM and exhibited also a good selectivity towards hBChE. The dissociation constants K-i of the selected inhibitors were compared with their IC50 values. Molecular modeling studies were performed to predict the binding modes between individual derivatives and hAChE/hBChE. (C) 2012 Elsevier Masson SAS. All rights reserved. New tacrine derivatives 5a-d, 6a-d with piperazino-ethyl spacer linked with corresponding secondary amines and tacrine homodimer 8 were synthesized and tested as cholinesterase inhibitors on human acetylcholinesterase (hAChE) and human plasmatic butyrylcholinesterase (hBChE). In most cases the majority of synthesized derivatives exhibit a high AChE and BChE inhibitory activity with IC50 values in the low-nanomolar range, being clearly more potent than the reference standard tacrine (9-amino-1,2,3,4-tetrahydroacridine, 1) and 7-MEOTA (7-methoxy-9-amino-1,2,3,4-tetrahydroacridine). Among them, inhibitors 8 and 5c, showed a strong inhibitory activity against hAChE, with an IC50 value of 4.49 nM and 4.97, nM resp., and a high selectivity to hAChE. The compound 5d acted as the most potent inhibitor against hBChE with an IC50 value of 33.7 nM and exhibited also a good selectivity towards hBChE. The dissociation constants K-i of the selected inhibitors were compared with their IC50 values. Molecular modeling studies were performed to predict the binding modes between individual derivatives and hAChE/hBChE. (C) 2012 Elsevier Masson SAS. All rights reserved. (en)
Title	Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease (en)
skos:prefLabel	Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease (en)
skos:notation	RIV/60162694:G44__/12:43874729!RIV13-GA0-G44_____
http://linked.open...avai/riv/aktivita	P
http://linked.open...avai/riv/aktivity	P(GAP303/11/1907)
http://linked.open...iv/cisloPeriodika	september
http://linked.open...vai/riv/dodaniDat	2013
http://linked.open...aciTvurceVysledku	Hrabinová, Martina Kuča, Kamil
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ministerstvo obrany / Univerzita obrany - Fakulta vojenského zdravotnictví Hradec Králové
http://linked.open...dnocenehoVysledku	172948
http://linked.open...ai/riv/idVysledku	RIV/60162694:G44__/12:43874729
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Molecular modeling; Amyloid; AChE/BChE inhibitors; Tacrine; Alzheimer's disease (en)
http://linked.open.../riv/klicoveSlovo	Molecular modeling Alzheimer's disease AChE/BChE inhibitors Amyloid Tacrine
http://linked.open...odStatuVydavatele	FR - Francouzská republika
http://linked.open...ontrolniKodProRIV	[A7467C456C87]
http://linked.open...i/riv/nazevZdroje	European Journal of Medicinal Chemistry
http://linked.open...in/vavai/riv/obor	FR
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	7 (xsd:int)
http://linked.open...vavai/riv/projekt	Novel inhibitors of acetylcholinesterase derived from 7-MEOTA - potential Alzheimer´s disease drugs
http://linked.open...UplatneniVysledku	2012
http://linked.open...v/svazekPeriodika	55
http://linked.open...iv/tvurceVysledku	Hrabinová, Martina Kuča, Kamil Janovec, Ladislav Banasova, Maria Hamulakova, Slavka Imrich, Jan Kristian, Pavol
http://linked.open...ain/vavai/riv/wos	000309494100003
issn	0223-5234
number of pages	9 (xsd:int)
http://bibframe.org/vocab/doi	10.1016/j.ejmech.2012.06.051
http://localhost/t...ganizacniJednotka	G44
is http://linked.open...avai/riv/vysledek of	Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease

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