Design, Synthesis, and Biological Evaluation of 1-Benzylamino-2-hydroxyalkyl Derivatives as New Potential Disease-Modifying Multifunctional Anti-Alzheimer's Agents
| العنوان: | Design, Synthesis, and Biological Evaluation of 1-Benzylamino-2-hydroxyalkyl Derivatives as New Potential Disease-Modifying Multifunctional Anti-Alzheimer's Agents |
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| المؤلفون: | Anna Pasieka, Ondrej Soukup, Jan Korabecny, Vendula Sepsova, Marek Bajda, Dawid Panek, Justyna Godyń, Anna Więckowska, Damijan Knez, Anja Pišlar, Stanislav Gobec, Jakub Jończyk, Tomasz Wichur, Janko Kos, Barbara Malawska, Raimon Sabaté |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, Cognitive Neuroscience, Tau protein, tau Proteins, Disease, Pharmacology, Biochemistry, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Derivative (finance), Alzheimer Disease, Humans, Butyrylcholinesterase, Biological evaluation, Amyloid beta-Peptides, Anti alzheimer, biology, Drug discovery, Chemistry, Cell Biology, General Medicine, Peptide Fragments, Molecular Docking Simulation, 030104 developmental biology, Design synthesis, Drug Design, biology.protein, Cholinesterase Inhibitors, 030217 neurology & neurosurgery |
| الوصف: | The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer’s disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, β-secretase, β-amyloid, and tau protein aggregation, all related to mechanisms which underpin Alzheimer’s disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets, inhibition of β-secretase (IC50 hBACE-1 = 41.60 μM), inhibition of amyloid β aggregation (IC50 Aβ = 3.09 μM), inhibition of tau aggregation (55% at 10 μM); as well as against symptomatic targets, butyrylcholinesterase inhibition (IC50 hBuChE = 7.22 μM). It might represent an encouraging starting point for development of multifunctional disease-modifying anti-Alzheimer’s agents. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d56bbac15f27d1a261c124235d35b847 https://ruj.uj.edu.pl/xmlui/handle/item/118051 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d56bbac15f27d1a261c124235d35b847 |
| قاعدة البيانات: | OpenAIRE |
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