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dc.creatorKrunić, Mihajlo
dc.creatorPenjišević, Jelena
dc.creatorSuručić, Relja
dc.creatorŠegan, Sandra
dc.creatorKostić-Rajačić, Slađana
dc.creatorJevtić, Ivana
dc.date.accessioned2023-01-25T10:37:23Z
dc.date.available2023-01-25T10:37:23Z
dc.date.issued2023
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.urihttps://cer.ihtm.bg.ac.rs/handle/123456789/5634
dc.description.abstractFourteen novel N-benzylpiperidine and N,N-diarylpiperazine conjugates were synthesized and pharmacologically evaluated as donepezil analogs, in a ligand-based drug design approach. All compounds possessed high to moderate in vitro inhibitory activity with IC50 in range 2.3–20 µM and selectivity towards acetylcholinesterase, while being inactive towards butyrylcholinesterase. Structure-activity relationship analysis revealed the influence of N,N-diarylpiperazine moiety and the linker connecting two pharmacophores on the inhibitory activity. Kinetic studies on the two most active compounds 7g and 8g (IC50 = 2.3 and 4 µM, respectively) revealed mixed type mode of inhibition, binding to both, free enzyme and enzyme-substrate complex. For further understanding of mechanism of action and binding orientations, molecular docking was performed for all compounds, while the ligand transport simulation and molecular dynamics simulations were performed for 7g and 8g. Computational results corroborated well with in vitro activities and kinetic studies.sr
dc.language.isoensr
dc.publisherElsevier B.V.sr
dc.relationinfo:eu-repo/grantAgreement/MESTD/inst-2020/200026/RS//sr
dc.rightsrestrictedAccesssr
dc.sourceJournal of Molecular Structuresr
dc.subjectAlzheimer's diseasesr
dc.subjectArylpiperazinesr
dc.subjectCholinesterasesr
dc.subjectLigand transport simulationsr
dc.subjectMolecular dockingsr
dc.subjectMolecular dynamicssr
dc.subjectN-benzylpiperidinesr
dc.titleStructure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitorssr
dc.typearticlesr
dc.rights.licenseARRsr
dc.citation.volume1276
dc.citation.spage134809
dc.citation.rankM22~
dc.identifier.doi10.1016/j.molstruc.2022.134809
dc.identifier.scopus2-s2.0-85145591644
dc.identifier.wos000904118100004
dc.type.versionpublishedVersionsr


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