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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.issued2018en_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.21481en_US
dc.identifier.issn0272-4391
dc.identifier.issn1098-2299
dc.identifier.urihttps://dx.doi.org/10.1002/ddr.21481
dc.identifier.urihttps://hdl.handle.net/20.500.12511/1836
dc.descriptionWOS: 000453476000005en_US
dc.descriptionPubMed ID: 30343499en_US
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.en_US
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.language.isoengen_US
dc.publisherWileyen_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectAcetylcholinesteraseen_US
dc.subjectAlzheimeren_US
dc.subjectPiperazineen_US
dc.subjectThiazoleen_US
dc.titleThiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitorsen_US
dc.typearticleen_US
dc.relation.journalDrug Development Researchen_US
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalıen_US
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Temel Eczacılık Bilimleri Bölümü, Farmasötik Mikrobiyoloji Ana Bilim Dalıen_US
dc.authorid0000-0002-5976-676Xen_US
dc.authorid0000-0002-2289-7950en_US
dc.authorid0000-0001-6047-2796en_US
dc.authorid0000-0003-1896-2729en_US
dc.authorid0000-0002-0841-1299en_US
dc.identifier.volume79en_US
dc.identifier.issue8en_US
dc.identifier.startpage406en_US
dc.identifier.endpage425en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1002/ddr.21481en_US


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