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dc.creatorBondžić, Aleksandra
dc.creatorSenćanski, Milan V.
dc.creatorVujačić Nikezić, Ana V.
dc.creatorKirillova, Marina V.
dc.creatorAndré, Vânia
dc.creatorKirillov, Alexander M.
dc.creatorBondžić, Bojan
dc.date.accessioned2020-12-03T12:15:04Z
dc.date.available2020-12-03T12:15:04Z
dc.date.issued2020
dc.identifier.issn0162-0134
dc.identifier.urihttps://cer.ihtm.bg.ac.rs/handle/123456789/3958
dc.description.abstractThree coordination compounds featuring different types of tetracopper(II) cores, namely [O⊂Cu4{N(CH2CH2O)3}4(BOH)4][BF4]2 (1), [Cu4(μ4-H2edte)(μ5-H2edte)(sal)2]n·7nH2O, (H4edte=N,N,N′, N′-tetrakis(2-hydroxyethyl)ethylenediamine, H2sal=salicylic acid) (2), and [{Cu4(μ3-Hbes)4(μ-hba)}K (H2O)3]n, H3bes=N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (3), were assayed for their potency to inhibit the acetyl (AChE) and butyrylcholinesterase (BuChE) enzymes aiming to test these compounds as potential dual inhibitors in the treatment of Alzheimer's disease. All the investigated compounds showed a strong inhibitory potency toward both enzymes with IC50 values in micromolar range of concentration; compound 1 displayed the most potent inhibitory behaviour toward both enzymes. The mechanism of the AChE and BuChE inhibition was examined by enzyme kinetic measurements. The obtained kinetic parameters, Vmax and Km indicated an uncompetitive type of inhibition of both enzymes by compound 1. For the other two compounds a non-competitive inhibition mode was observed. To get further insight into the mechanism of action and to elucidate binding modes in details we examined the interactions of 1–3 with acetylcholinesterase, using molecular docking approach. Grid based docking studies indicated that these compounds can bind to peripheral anionic site (PAS) of the AChE with Ki values in micromolar range. Moreover, blind docking revealed the capability of investigated compounds to bind to new allosteric site (i.e. binding site II) distinct from PAS. Showing that these Cu-based compounds can act as new allosteric inhibitors of AChE and identifying novel allosteric binding site on AChE represents a significant contribution toward the design of novel and more effective inhibitors of AChE.en
dc.language.isoensr
dc.publisherElseviersr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172023/RS//sr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173001/RS//sr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172020/RS//sr
dc.relationFoundation for Science and Technology (FCT) and Portugal 2020 (projects LISBOA-01-0145- FEDER-029697)sr
dc.relationFoundation for Science and Technology (FCT) and Portugal 2020 ( IF/01395/2013/CP1163/CT005)sr
dc.relationFoundation for Science and Technology (FCT) and Portugal 2020 (CEECIND/03708/ 2017)sr
dc.relationFoundation for Science and Technology (FCT) and Portugal 2020 (UIDB/00100/2020)sr
dc.relationFoundation for Science and Technology (FCT) and Portugal 2020 (SFRH/BSAB/150368)sr
dc.relationRUDN University Program 5-100sr
dc.relationEU COST Action CA15135 (MuTaLig)sr
dc.relationEU COST Action CA15106 (CHAOS)sr
dc.rightsrestrictedAccesssr
dc.sourceJournal of Inorganic Biochemistrysr
dc.subjectAChEsr
dc.subjectBuChEsr
dc.subjectDual inhibitorssr
dc.subjectDocking studiessr
dc.titleAminoalcoholate-driven tetracopper(II) cores as dual acetyl and butyrylcholinesterase inhibitors: Experimental and theoretical elucidation of mechanism of actionen
dc.typearticlesr
dc.rights.licenseARRsr
dcterms.abstractБонджић, Бојан; Бонджић, Aлександра; Сенћански, Милан В.; Кириллов, Aлеxандер М.; Aндрé, Вâниа; Вујачић Никезић, Aна В.; Кириллова, Марина В.;
dc.rights.holderElseviersr
dc.citation.volume205
dc.citation.spage110990
dc.citation.rankM21~
dc.identifier.pmid32035286
dc.identifier.doi10.1016/j.jinorgbio.2019.110990
dc.identifier.scopus2-s2.0-85078834022
dc.identifier.wos000522119300020
dc.type.versionpublishedVersionsr


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