About: Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers

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About: Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://www.sciencedirect.com/science/article/pii/S0141813014004826#
Description	A new series of substituted tacrine/acridine and tacrine/tacrine dimers with aliphatic or alkylene-thiourea linkers was synthesized and the potential of these compounds as novel human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE) inhibitors with nanomolar inhibition activity was evaluated. The most potent AChE inhibitor was found to be homodimeric tacrine derivative 14a, which demonstrated an IC50 value of 2 nM; this value indicates an activity rate which is 250-times higher than that of tacrine 1 and 7500-times higher than 7-MEOTA 15, the compounds which were used as standards in the study. IC50 values of derivatives 1, 9, 10, 14b and 15 were compared with the dissociation constants of the enzyme-inhibitor complex, K-i1, and the enzyme-substrate-inhibitor complex, K-i2, for. A dual binding site is presumed for the synthesized compounds which possess two tacrines or tacrine and acridine as terminal moieties show evidence of dual site binding. DFT calculations of theoretical desolvation free energies, Delta Delta G(theor), and docking studies elucidate these suggestions in more detail. A new series of substituted tacrine/acridine and tacrine/tacrine dimers with aliphatic or alkylene-thiourea linkers was synthesized and the potential of these compounds as novel human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE) inhibitors with nanomolar inhibition activity was evaluated. The most potent AChE inhibitor was found to be homodimeric tacrine derivative 14a, which demonstrated an IC50 value of 2 nM; this value indicates an activity rate which is 250-times higher than that of tacrine 1 and 7500-times higher than 7-MEOTA 15, the compounds which were used as standards in the study. IC50 values of derivatives 1, 9, 10, 14b and 15 were compared with the dissociation constants of the enzyme-inhibitor complex, K-i1, and the enzyme-substrate-inhibitor complex, K-i2, for. A dual binding site is presumed for the synthesized compounds which possess two tacrines or tacrine and acridine as terminal moieties show evidence of dual site binding. DFT calculations of theoretical desolvation free energies, Delta Delta G(theor), and docking studies elucidate these suggestions in more detail. (en)
Title	Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers (en)
skos:prefLabel	Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers (en)
skos:notation	RIV/60162694:G44__/14:43875136!RIV15-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	2015
http://linked.open...aciTvurceVysledku	Kuča, Kamil Pohanka, Doc. RNDr. PhD, Miroslav
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	33119
http://linked.open...ai/riv/idVysledku	RIV/60162694:G44__/14:43875136
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Cholinesterase; beta-Amyloid aggregation; Tacrine; Coumarin; Cholinesterase inhibitors; Alzheimer's disease (en)
http://linked.open.../riv/klicoveSlovo	Cholinesterase Coumarin Alzheimer's disease Tacrine Cholinesterase inhibitors beta-Amyloid aggregation
http://linked.open...odStatuVydavatele	NL - Nizozemsko
http://linked.open...ontrolniKodProRIV	[9B82BB74FEF5]
http://linked.open...i/riv/nazevZdroje	International Journal of Biological Macromolecules
http://linked.open...in/vavai/riv/obor	CE
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	10 (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	2014
http://linked.open...v/svazekPeriodika	70
http://linked.open...iv/tvurceVysledku	Kuča, Kamil Pohanka, Miroslav Janovec, Ladislav Holas, Ondřej Kristian, Pavol Imrich, Ján Danihel, Ivan Bohm, Stanislav Hamul'áková, Slávka Kozurková, Mária
http://linked.open...ain/vavai/riv/wos	000342478800061
issn	0141-8130
number of pages	5 (xsd:int)
http://bibframe.org/vocab/doi	10.1016/j.ijbiomac.2014.06.064
http://localhost/t...ganizacniJednotka	G44

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