Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors
| Autor: | Zafer Şahin, Barkın Berk, Merve Ertaş, Sevde Nur Biltekin, Şeref Demirayak, Emre F. Bülbül, Ceysu Bender, Leyla Yurttaş |
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| Přispěvatelé: | Sahin, Zafer, Ertas, Merve, Berk, Barkin, Demirayak, Seref Istanbul Medipol Univ, Sch Pharm, Dept Pharmaceut Chem, TR-34083 Istanbul, Turkey, Biltekin, Sevde N. Istanbul Medipol Univ, Sch Pharm, Dept Pharmaceut Microbiol, Istanbul, Turkey, Yurttas, Leyla Anadolu Univ, Dept Pharmaceut Chem, Fac Pharm, Eskisehir, Turkey, BULBUL, Emre Fatih -- 0000-0002-9901-2022, Berk, Barkin -- 0000-0001-6047-2796, Anadolu Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, Demirayak, Şeref |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular Synaptic cleft Pharmacology 01 natural sciences chemistry.chemical_compound Drug Discovery medicine Galantamine Humans Donepezil Thiazole Rivastigmine 010405 organic chemistry Biological activity acetylcholinesterase piperazine Acetylcholinesterase 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Thiazoles chemistry Tacrine Alzheimer Cholinesterase Inhibitors thiazole medicine.drug |
| Popis: | WOS: 000453476000005 PubMed ID: 30343499 Hit, 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. Anatolian University Scientific Research Projects Coordination Unit [1610S656] This project was financially supported by the Anatolian University Scientific Research Projects Coordination Unit 1610S656. |
| Databáze: | OpenAIRE |
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