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dc.creatorVitorović-Todorović, Maja D.
dc.creatorKoukoulitsa, Catherine
dc.creatorJuranić, Ivan
dc.creatorMandić, Ljuba M.
dc.creatorDrakulić, Branko
dc.date.accessioned2019-10-11T21:45:31Z
dc.date.available2015-05-04
dc.date.issued2014
dc.identifier.issn0223-5234
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/3134
dc.description.abstractCongeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.en
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier, Paris
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/261499/EU//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS//
dc.rightsembargoedAccess
dc.sourceEuropean Journal of Medicinal Chemistry
dc.subject4-Aryl-4-oxo-2-aminylbutyramidesen
dc.subjectAnticholinesterase activityen
dc.subjectMixed type reversible inhibitorsen
dc.subjectDocking studyen
dc.subjectMolecular dynamicsen
dc.titleStructural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulationsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractМандић, Љуба М.; Јуранић, Иван; Коукоулитса, Цатхерине; Виторовић-Тодоровић, Маја Д.; Дракулић, Бранко;
dc.citation.volume81
dc.citation.spage158
dc.citation.epage175
dc.citation.other81: 158-175
dc.citation.rankM21
dc.description.otherThis is the peer-reviewed version of the article: Vitorović-Todorović, M. D.; Koukoulitsa, C.; Juranić, I. O.; Mandić, L. M.; Drakulić, B. J. Structural Modifications of 4-Aryl-4-Oxo-2-Aminylbutanamides and Their Acetyl- and Butyrylcholinesterase Inhibitory Activity. Investigation of AChE-Ligand Interactions by Docking Calculations and Molecular Dynamics Simulations. European Journal of Medicinal Chemistry 2014, 81, 158–175. [https://doi.org/10.1016/j.ejmech.2014.05.008]
dc.description.other[http://cer.ihtm.bg.ac.rs/handle/123456789/2688]
dc.identifier.pmid24836068
dc.identifier.doi10.1016/j.ejmech.2014.05.008
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs/bitstream/id/14132/j.ejmech.2014.05.008.pdf
dc.identifier.scopus2-s2.0-84900870587
dc.identifier.wos000338598400015
dc.type.versionacceptedVersionen


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