Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors

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dc.authorid0000-0002-5976-676X
dc.authorid0000-0002-2289-7950
dc.authorid0000-0001-6047-2796
dc.authorid0000-0003-1896-2729
dc.authorid0000-0002-0841-1299
dc.contributor.authorŞahin, Zafer
dc.contributor.authorErtaş, Merve
dc.contributor.authorBender, Ceysu
dc.contributor.authorBülbül, Emre Fatih
dc.contributor.authorBerk, Barkın
dc.contributor.authorBiltekin, Sevde Nur
dc.contributor.authorYurttaş, Leyla
dc.contributor.authorDemirayak, Şeref
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:49:58Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:49:58Z
dc.date.issued2018
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.descriptionWOS: 000453476000005
dc.descriptionPubMed ID: 30343499
dc.description.abstractHit, Lead & Candidate Discovery After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid-20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic-framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified. The aim of this study was to design new donepezil analogs. In this study, 66 original piperazinyl thiazole derivatives were synthesized by the reaction of piperazine N '-benzoyl thioamides and bromoacetophenones to inhibit AChE. Biological activity was measured by the Ellman method. Compounds 35, 38, 40, 45, 57, and 61 showed a high inhibitory effect among the series (80.36%-83.94% inhibition), and donepezil had a 96.42% inhibitory effect. The IC50 values of compounds 35, 38, and 40, were calculated as 0.9767 mu M, 0.9493 mu M, and 0.8023 mu M, respectively. Compound 45 (IC50 = 1.122), Compound 57 (IC50 = 1.2130) and 61 (IC50 = 0.9193) also exhibited good activity on AChE. Molecular modeling studies were in agreement with the predictions. Trp286, Arg296, and Tyr341 were the key amino acids at the active site. Both donepezil and synthesized compounds seemed to interact with these residues.
dc.description.sponsorshipAnatolian University Scientific Research Projects Coordination Unit [1610S656]en_US
dc.description.sponsorshipThis project was financially supported by the Anatolian University Scientific Research Projects Coordination Unit 1610S656.en_US
dc.identifier.citationŞahin, Z., Ertaş, M., Bender, C., Bülbül, E. F., Berk, B., Biltekin, S. ... Demirayak, Ş. (2018). Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors. Drug Development Research, 79(8), 406-425. https://dx.doi.org/10.1002/ddr.21481
dc.identifier.doi10.1002/ddr.21481
dc.identifier.endpage425
dc.identifier.issn0272-4391
dc.identifier.issn1098-2299
dc.identifier.issue8
dc.identifier.scopusqualityQ2
dc.identifier.startpage406
dc.identifier.urihttps://dx.doi.org/10.1002/ddr.21481
dc.identifier.urihttps://hdl.handle.net/20.500.12511/1836
dc.identifier.volume79
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofDrug Development Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAcetylcholinesterase
dc.subjectAlzheimer
dc.subjectPiperazine
dc.subjectThiazole
dc.titleThiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors
dc.typeArticle

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