Design, Synthesis, and Biological Evaluation of 1-Benzylamino-2-hydroxyalkyl Derivatives as New Potential Disease-Modifying Multifunctional Anti-Alzheimer's Agents
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- Klíčová slova
- Alzheimer’s disease, Aβ aggregation, BACE-1 inhibitors, butyrylcholinesterase inhibitors, molecular docking, multifunctional agents, tau aggregation,
- MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- amyloidní beta-protein účinky léků metabolismus MeSH
- butyrylcholinesterasa farmakologie MeSH
- cholinesterasové inhibitory farmakologie MeSH
- lidé MeSH
- peptidové fragmenty metabolismus MeSH
- proteiny tau účinky léků MeSH
- racionální návrh léčiv * MeSH
- simulace molekulového dockingu metody MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amyloidní beta-protein MeSH
- butyrylcholinesterasa MeSH
- cholinesterasové inhibitory MeSH
- peptidové fragmenty MeSH
- proteiny tau MeSH
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.
Citace poskytuje Crossref.org
Sustainable Drug Discovery of Multi-Target-Directed Ligands for Alzheimer's Disease
