Novel thiazole-piperazine derivatives as potential cholinesterase inhibitors

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dc.authorid0000-0002-5976-676X
dc.authorid0000-0002-2289-7950
dc.authorid0000-0001-6047-2796
dc.contributor.authorDemirayak, Şeref
dc.contributor.authorŞahin, Zafer
dc.contributor.authorErtaş, Merve
dc.contributor.authorBülbül, Emre Fatih
dc.contributor.authorBender, Ceysu
dc.contributor.authorBiltekin, Sevde Nur
dc.contributor.authorBerk, Barkın
dc.contributor.authorSağlık, Begüm Nurpelin
dc.contributor.authorLevent, Serkan
dc.contributor.authorYurttaş, Leyla
dc.date.accessioned2019-12-26T07:18:27Z
dc.date.available2019-12-26T07:18:27Z
dc.date.issued2019
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Temel Eczacılık Bilimleri Bölümü, Farmasötik Mikrobiyoloji Ana Bilim Dalı
dc.description.abstractDementia is a cognitive disorder mostly associated with Alzheimer's disease (AD) in addition to being seen in many other diseases of the central nervous system (CNS). The limited number of drugs is not sufficient to provide adequate improvement to increase the quality of life of patients suffering from this symptom; therefore, all treatment options should be evaluated in detail. In this study, new molecules, [2-(4-(2/3/4-substituted phenyl)piperazin-1-yl)-4-phenylthiazol-5-yl][3/4-substituted phenyl]methanone derivatives (1-44), were obtained and analyzed in terms of their anticholinesterase activities. Kinetic mode and molecular interactions were also evaluated. An enzyme inhibition study was undertaken on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the Ellman method. Maestro program was used in molecular modeling studies. Forty-four compounds were evaluated on AChE and BChE enzymes at 10(-3) and 10(-4) concentrations. The inhibition concentrations were calculated as 0.268 mu M to 2.104 mu M for six compounds (4, 5, 16, 27, 37, and 38) on AChE. Compound 5 including the 4-methoxy substituent (IC50: 0.268 mu M) and compound 38 containing the 4-methoxy and 3-methyl substituents (IC50: 0.286 mu M) showed the highest AChE inhibitory activity. They were further examined in terms of hydrogen bonding with Arg296 and Ar-Ar interaction with Trp286. The activity of compound 5 was also assessed in mixed-type kinetic mode.
dc.identifier.citationDemirayak, Ş., Şahin, Z., Ertaş, M., Bülbül, E. F., Bender, C., Biltekin, S. N. ... Yurttaş, L. (2019). Novel thiazole-piperazine derivatives as potential cholinesterase inhibitors. Journal of Heterocyclic Chemistry, 56(12), 3370-3386. https://doi.org/10.1002/jhet.3734
dc.identifier.doi10.1002/jhet.3734
dc.identifier.issn0022-152X
dc.identifier.issn1943-5193
dc.identifier.issue12
dc.identifier.scopusqualityQ3
dc.identifier.startpage3370
dc.identifier.startpage3386
dc.identifier.urihttps://doi.org/10.1002/jhet.3734
dc.identifier.urihttps://hdl.handle.net/20.500.12511/4711
dc.identifier.volume56
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofJournal of Heterocyclic Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectTarget-Directed Ligands
dc.subjectBiological Evaluation
dc.subjectAnticholinesterase Activity
dc.subjectMolecular Docking
dc.subjectIn-Silico
dc.subjectDesign
dc.subjectAcetylcholinesterase
dc.subjectButyrylcholinesterase
dc.subjectHybrids
dc.subjectDonepezil
dc.titleNovel thiazole-piperazine derivatives as potential cholinesterase inhibitors
dc.typeArticle

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